In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from one neuron to another,
playing a key role in enabling rapid and direct communication by
creating circuits. In addition, a synapse serves as a junction where
both the transmission and processing of information occur, making it a
vital means of communication between neurons.
Neurons are specialized to pass signals to individual target cells, and
synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery
that link the two membranes together and carry out the signaling
process. In many synapses, the presynaptic part is located on an axon and the postsynaptic part is located on a dendrite or soma. Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating neurotransmission.
Synapses (at least chemical synapses) are stabilized in position by
synaptic adhesion molecules (SAMs) projecting from both the pre- and
post-synaptic neuron and sticking together where they overlap; SAMs may
also assist in the generation and functioning of synapses.
Moreover, SAMs coordinate the formation of synapses, with various types
working together to achieve the remarkable specificity of synapses. In essence, SAMs function in both excitatory and inhibitory synapses, likely serving as devices for signal transmission.
History
Santiago Ramón y Cajal proposed that neurons are not continuous throughout the body, yet still communicate with each other, an idea known as the neuron doctrine. The word "synapse" was introduced in 1897 by the English neurophysiologist Charles Sherrington in Michael Foster's Textbook of Physiology. Sherrington struggled to find a good term that emphasized a union between two separate elements, and the actual term "synapse" was suggested by the English classical scholar Arthur Woollgar Verrall, a friend of Foster. The word was derived from the Greeksynapsis (σύναψις), meaning "conjunction", which in turn derives from synaptein (συνάπτειν), from syn (σύν) "together" and haptein (ἅπτειν) "to fasten".
However, while the synaptic gap remained a theoretical construct,
and was sometimes reported as a discontinuity between contiguous axonal
terminations and dendrites or cell bodies, histological methods using
the best light microscopes of the day could not visually resolve their
separation which is now known to be about 20 nm. It needed the electron
microscope in the 1950s to show the finer structure of the synapse with
its separate, parallel pre- and postsynaptic membranes and processes,
and the cleft between the two.
Chemical and electrical synapses are two ways of synaptic transmission.
In a chemical synapse, electrical activity in the presynaptic neuron is converted (via the activation of voltage-gated calcium channels) into the release of a chemical called a neurotransmitter that binds to receptors
located in the plasma membrane of the postsynaptic cell. The
neurotransmitter may initiate an electrical response or a secondary
messenger pathway that may either excite or inhibit the postsynaptic
neuron. Chemical synapses can be classified according to the
neurotransmitter released: glutamatergic (often excitatory), GABAergic (often inhibitory), cholinergic (e.g. vertebrate neuromuscular junction), and adrenergic (releasing norepinephrine). Because of the complexity of receptor signal transduction, chemical synapses can have complex effects on the postsynaptic cell.
In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by special channels called gap junctions
that are capable of passing an electric current, causing voltage
changes in the presynaptic cell to induce voltage changes in the
postsynaptic cell.In fact, gap junctions facilitate the direct flow of electrical current
without the need for neurotransmitters, as well as small molecules like
calcium. Thus, the main advantage of an electrical synapse is the rapid transfer of signals from one cell to the next.
Mixed chemical electrical synapses are synaptic sites that feature both a gap junction and neurotransmitter release. This combination allows a signal to have both a fast component (electrical) and a slow component (chemical).
The formation of neural circuits in nervous systems, appears to
heavily depend on the crucial interactions between chemical and
electrical synapses. Thus, these interactions govern the generation of
synaptic transmission. Synaptic communication is distinct from an ephaptic coupling, in which communication between neurons occurs via indirect electric fields. An autapse is a chemical or electrical synapse that forms when the axon of one neuron synapses onto dendrites of the same neuron.
Excitatory and inhibitory
Excitatory
synapse: Enhances the probability of depolarization in postsynaptic
neurons and the initiation of an action potential.
Inhibitory Synapse: Diminishes the probability of depolarization in
postsynaptic neurons and the initiation of an action potential.
An influx of Na+ driven by excitatory neurotransmitters opens cation
channels, depolarizing the postsynaptic membrane toward the action
potential threshold. In contrast, inhibitory neurotransmitters cause the
postsynaptic membrane to become less depolarized by opening either Cl-
or K+ channels, reducing firing. Depending on their release location,
the receptors they bind to, and the ionic circumstances they encounter,
various transmitters can be either excitatory or inhibitory. For
instance, acetylcholine can either excite or inhibit depending on the
type of receptors it binds to.
For example, glutamate serves as an excitatory neurotransmitter, in
contrast to GABA, which acts as an inhibitory neurotransmitter.
Additionally, dopamine is a neurotransmitter that exerts dual effects,
displaying both excitatory and inhibitory impacts through binding to
distinct receptors.
The membrane potential prevents Cl- from entering the cell, even
when its concentration is much higher outside than inside. The resting
potential for Cl- in many neurons is quite negative, nearly equal to the
resting potential. Opening Cl- channels tends to buffer the membrane
potential, but this effect is countered when the membrane starts to
depolarize, allowing more negatively charged Cl- ions to enter the cell.
Consequently, it becomes more difficult to depolarize the membrane and
excite the cell when Cl- channels are open. Similar effects result from
the opening of K+ channels. The significance of inhibitory
neurotransmitters is evident from the effects of toxins that impede
their activity. For instance, strychnine binds to glycine receptors,
blocking the action of glycine and leading to muscle spasms,
convulsions, and death.
Interfaces
Synapses
can be classified by the type of cellular structures serving as the
pre- and post-synaptic components. The vast majority of synapses in the
mammalian nervous system are classical axo-dendritic synapses (axon
synapsing upon a dendrite), however, a variety of other arrangements
exist. These include but are not limited to axo-axonic, dendro-dendritic, axo-secretory, axo-ciliary, somato-dendritic, dendro-somatic, and somato-somatic synapses.
In fact, the axon can synapse onto a dendrite, onto a cell body,
or onto another axon or axon terminal, as well as into the bloodstream
or diffusely into the adjacent nervous tissue.
Different types of synapses
Conversion of chemical into electrical signals
Neurotransmitters
are tiny signal molecules stored in membrane-enclosed synaptic vesicles
and released via exocytosis. Indeed, a change in electrical potential
in the presynaptic cell triggers the release of these molecules. By
attaching to transmitter-gated ion channels, the neurotransmitter causes
an electrical alteration in the postsynaptic cell and rapidly diffuses
across the synaptic cleft. Once released, the neurotransmitter is
swiftly eliminated, either by being absorbed by the nerve terminal that
produced it, taken up by nearby glial cells, or broken down by specific
enzymes in the synaptic cleft. Numerous Na+-dependent neurotransmitter
carrier proteins recycle the neurotransmitters and enable the cells to
maintain rapid rates of release.
At chemical synapses, transmitter-gated ion channels play a vital
role in rapidly converting extracellular chemical impulses into
electrical signals. These channels are located in the postsynaptic
cell's plasma membrane at the synapse region, and they temporarily open
in response to neurotransmitter molecule binding, causing a momentary
alteration in the membrane's permeability. Additionally,
transmitter-gated channels are comparatively less sensitive to the
membrane potential than voltage-gated channels, which is why they are
unable to generate self-amplifying excitement on their own. However,
they result in graded variations in membrane potential due to local
permeability, influenced by the amount and duration of neurotransmitter
released at the synapse.
Release of neurotransmitters
Neurotransmitters bind to ionotropic receptors on postsynaptic neurons, either causing their opening or closing.
The variations in the quantities of neurotransmitters released from the
presynaptic neuron may play a role in regulating the effectiveness of
synaptic transmission. In fact, the concentration of cytoplasmic calcium
is involved in regulating the release of neurotransmitters from
presynaptic neurons.
The chemical transmission involves several sequential processes:
Synthesizing neurotransmitters within the presynaptic neuron.
Loading the neurotransmitters into secretory vesicles.
Controlling the release of neurotransmitters into the synaptic cleft.
Binding of neurotransmitters to postsynaptic receptors.
Ceasing the activity of the released neurotransmitters.
Synaptic polarization
The function of neurons depends upon cell polarity. The distinctive structure of nerve cells allows action potentials
to travel directionally (from dendrites to cell body down the axon),
and for these signals to then be received and carried on by
post-synaptic neurons or received by effector cells. Nerve cells have
long been used as models for cellular polarization, and of particular
interest are the mechanisms underlying the polarized localization of
synaptic molecules. PIP2 signaling regulated by IMPase plays an integral role in synaptic polarity.
Phosphoinositides (PIP, PIP2, and PIP3) are molecules that have been shown to affect neuronal polarity. A gene (ttx-7) was identified in Caenorhabditis elegans that encodes myo-inositol monophosphatase (IMPase), an enzyme that produces inositol by dephosphorylatinginositol phosphate. Organisms with mutant ttx-7
genes demonstrated behavioral and localization defects, which were
rescued by expression of IMPase. This led to the conclusion that IMPase
is required for the correct localization of synaptic protein components. The egl-8 gene encodes a homolog of phospholipase Cβ (PLCβ), an enzyme that cleaves PIP2. When ttx-7 mutants also had a mutant egl-8 gene, the defects caused by the faulty ttx-7
gene were largely reversed. These results suggest that PIP2 signaling
establishes polarized localization of synaptic components in living
neurons.
Presynaptic modulation
Modulation of neurotransmitter release by G-protein-coupled receptors (GPCRs) is a prominent presynaptic mechanism for regulation of synaptic transmission.
The activation of GPCRs located at the presynaptic terminal, can
decrease the probability of neurotransmitter release. This presynaptic
depression involves activation of Gi/o-type G-proteins that mediate different inhibitory mechanisms, including inhibition of voltage-gated calcium channels, activation of potassium channels, and direct inhibition of the vesicle fusion process. Endocannabinoids, synthesized in and released from postsynaptic neuronal elements, and their cognate receptors, including the (GPCR) CB1 receptor, located at the presynaptic terminal, are involved in this modulation by an retrograde signaling
process, in which these compounds are synthesized in and released from
postsynaptic neuronal elements, and travel back to the presynaptic
terminal to act on the CB1 receptor for short-term or long-term synaptic
depression, that cause a short or long lasting decrease in
neurotransmitter release.
Effects of drugs on ligand-gated ion channels
Drugs
have long been considered crucial targets for transmitter-gated ion
channels. The majority of medications utilized to treat schizophrenia,
anxiety, depression, and sleeplessness work at chemical synapses, and
many of these pharmaceuticals function by binding to transmitter-gated
channels. For instance, some drugs like barbiturates and tranquilizers
bind to GABA receptors and enhance the inhibitory effect of GABA
neurotransmitter. Thus, reduced concentration of GABA enables the
opening of Cl- channels.
Furthermore, psychoactive drugs could potentially target many
other synaptic signalling machinery components. In fact, numerous
neurotransmitters are released by Na+-driven carriers and are
subsequently removed from the synaptic cleft. By inhibiting such
carriers, synaptic transmission is strengthened as the action of the
transmitter is prolonged. For example, Prozac is one of antidepressant
medications that works by preventing the absorption of serotonin
neurotransmitter. Also, other antidepressants operate by inhibiting the
reabsorption of both serotonin and norepinephrine.
Biogenesis
In
nerve terminals, synaptic vesicles are produced quickly to compensate
for their rapid depletion during neurotransmitter release. Their
biogenesis involves segregating synaptic vesicle membrane proteins from
other cellular proteins and packaging those distinct proteins into
vesicles of appropriate size. Besides, it entails the endocytosis of
synaptic vesicle membrane proteins from the plasma membrane.
Synaptoblastic and synaptoclastic refer to
synapse-producing and synapse-removing activities within the biochemical
signalling chain. This terminology is associated with the Bredesen Protocol for treating Alzheimer's disease,
which conceptualizes Alzheimer's as an imbalance between these
processes. As of October 2023, studies concerning this protocol remain
small and few results have been obtained within a standardized control
framework.
It is widely accepted that the synapse plays a key role in the formation of memory.
The stability of long-term memory can persist for many years;
nevertheless, synapses, the neurological basis of memory, are very
dynamic.
The formation of synaptic connections significantly depends on
activity-dependent synaptic plasticity observed in various synaptic
pathways. Indeed, the connection between memory formation and
alterations in synaptic efficacy enables the reinforcement of neuronal
interactions between neurons. As neurotransmitters activate receptors
across the synaptic cleft, the connection between the two neurons is
strengthened when both neurons are active at the same time, as a result
of the receptor's signaling mechanisms. The strength of two connected
neural pathways is thought to result in the storage of information,
resulting in memory. This process of synaptic strengthening is known as long-term potentiation (LTP).
By altering the release of neurotransmitters, the plasticity of
synapses can be controlled in the presynaptic cell. The postsynaptic
cell can be regulated by altering the function and number of its
receptors. Changes in postsynaptic signaling are most commonly
associated with a N-methyl-d-aspartic acid receptor (NMDAR)-dependent LTP and long-term depression
(LTD) due to the influx of calcium into the post-synaptic cell, which
are the most analyzed forms of plasticity at excitatory synapses.
Mechanism of protein kinase
Moreover,
Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is best
recognized for its roles in the brain, particularly in the neocortex and
hippocampal regions because it serves as a ubiquitous mediator of
cellular Ca2+ signals. CaMKII is abundant in the nervous system, mainly
concentrated in the synapses in the nerve cells. Indeed, CaMKII has been
definitively identified as a key regulator of cognitive processes, such
as learning, and neural plasticity. The first concrete experimental
evidence for the long-assumed function of CaMKII in memory storage was
demonstrated
While Ca2+/CaM binding stimulates CaMKII activity,
Ca2+-independent autonomous CaMKII activity can also be produced by a
number of other processes. CaMKII becomes active by autophosphorylating
itself upon Ca2+/calmodulin binding. CaMKII is still active and
phosphorylates itself even after Ca2+ is cleaved; as a result, the brain
stores long-term memories using this mechanism. Nevertheless, when the
CaMKII enzyme is dephosphorylated by a phosphatase enzyme, it becomes
inactive, and memories are lost. Hence, CaMKII plays a vital role in
both the induction and maintenance of LTP.
Experimental models
For technical reasons, synaptic structure and function have been historically studied at unusually large model synapses, for example:
Schaffer collateral synapses in the hippocampus. These synapses are small, but their pre- and postsynaptic neurons are well separated (CA3 and CA1, respectively).
Synapses and Diseases
Synapses
function as ensembles within particular brain networks to control the
amount of neuronal activity, which is essential for memory, learning,
and behavior. Consequently, synaptic disruptions might have negative
effects. In fact, alterations in cell-intrinsic molecular systems or
modifications to environmental biochemical processes can lead to
synaptic dysfunction. The synapse is the primary unit of information
transfer in the nervous system, and correct synaptic contact creation
during development is essential for normal brain function. In addition,
several mutations have been connected to neurodevelopmental disorders,
and that compromised function at different synapse locations is a
hallmark of neurodegenerative diseases.
Synaptic defects are causally associated with early appearing
neurological diseases, including autism spectrum disorders (ASD),
schizophrenia (SCZ), and bipolar disorder (BP). On the other hand, in
late-onset degenerative pathologies, such as Alzheimer's (AD),
Parkinson's (PD), and Huntington's (HD) diseases, synaptopathy is
thought to be the inevitable end-result of an ongoing pathophysiological
cascade. These diseases are identified by a gradual loss in cognitive
and behavioral function and a steady loss of brain tissue. Moreover,
these deteriorations have been mostly linked to the gradual build-up of
protein aggregates in neurons, the composition of which may vary based
on the pathology; all have the same deleterious effects on neuronal
integrity. Furthermore, the high number of mutations linked to synaptic
structure and function, as well as dendritic spine alterations in
post-mortem tissue, has led to the association between synaptic defects
and neurodevelopmental disorders, such as ASD and SCZ, characterized by
abnormal behavioral or cognitive phenotypes.
Nevertheless, due to limited access to human tissue at late
stages and a lack of thorough assessment of the essential components of
human diseases in the available experimental animal models, it has been
difficult to fully grasp the origin and role of synaptic dysfunction in
neurological disorders.
Additional images
Diagram of the synapse. Please see learnbio.org for interactive version
Brain connectivity estimators represent patterns of links in the brain. Connectivity can be considered at different levels of the brain's organisation: from neurons, to neural assemblies
and brain structures. Brain connectivity involves different concepts
such as: neuroanatomical or structural connectivity (pattern of
anatomical links), functional connectivity (usually understood as statistical dependencies) and effective connectivity (referring to causal interactions).
Neuroanatomical connectivity is inherently difficult to define
given the fact that at the microscopic scale of neurons, new synaptic
connections or elimination of existing ones are formed dynamically and
are largely dependent on the function executed, but may be considered as
pathways extending over regions of the brain, which are in accordance
with general anatomical knowledge. Diffusion Weighted Imaging
(DWI) can be used to provide such information.
The distinction between functional and effective connectivity is not
always sharp; sometimes causal or directed connectivity is called
functional connectivity. Functional connectivity, may be defined as the
temporal correlation (in terms of statistically significant dependence
between distant brain regions) among the activity of different neural
assemblies, whereas effective connectivity may be defined as the direct
or indirect influence that one neural system exerts over another.
Some brain connectivity estimators evaluate connectivity from brain activity time series such as Electroencephalography (EEG), Local field potential (LFP) or spike trains, with an effect on the directed connectivity. These estimators can be applied to fMRI data, if the required image sequences are available.
Among estimators of connectivity, there are linear
and non-linear, bivariate and multivariate measures. Certain estimators
also indicate directionality. Different methods of connectivity
estimation vary in their effectiveness.This article provides an overview of these measures, with an emphasis on the most effective methods.
Bi-variate estimators
Classical methods
Classical estimators of connectivity are correlation and coherence. The above measures provide information on the directionality of interactions in terms of delay (correlation) or coherence (phase),
however the information does not imply causal interaction. Moreover, it
may be ambiguous, since phase is determined modulo 2π. It is also not
possible to identify by means of correlation or coherence.
Non-linear methods
The most frequently used nonlinear estimators of connectivity are mutual information, transfer entropy, generalised synchronisation, the continuity measure, synchronization likelihood, and phase synchronization. Mutual information and transfer entropy rely on the construction of histograms
for probability estimates. The continuity measure, generalized
synchronisations, and synchronisation likelihood are very similar
methods based on phase space
reconstruction. Among these measures, only transfer entropy allows for
the determination of directionality. Nonlinear measures require long
stationary segments of signals, are prone to systematic errors, and
above all are very sensitive to noise. The comparison of nonlinear methods with linear correlation in the presence of noise reveals the poorer performance of non-linear estimators. In the authors conclude that there must be good reason to think that there
is non-linearity in the data to apply non-linear methods. In fact it
was demonstrated by means of surrogate data test, and time series forecasting
that nonlinearity in EEG and LFP is the exception rather than the norm.
On the other hand, linear methods perform quite well for non-linear
signals. Finally, non-linear methods are bivariate (calculated pair-wise), which has serious implication on their performance.
Bivariate versus multivariate estimators
Comparison of performance of bivariate and multivariate estimators of connectivity may be found in,where it was demonstrated that in case of interrelated system of
channels, greater than two, bivariate methods supply misleading
information, even reversal of true propagation may be found.
Consider the very common situation that the activity from a given source
is measured at electrodes positioned at different distances, hence
different delays between the recorded signals.
When a bivariate measure is applied, propagation is always obtained when there is a delay between channels,
which results in a lot of spurious flows. When we have two or three
sources acting simultaneously, which is a common situation, we shall get
dense and disorganized structure of connections, similar to random
structure (at best some "small world" structure may be identified). This
kind of pattern is usually obtained in case of application of bivariate
measures. In fact, effective connectivity patterns yielded by EEG or
LFP measurements are far from randomness, when proper multivariate
measures are applied, as we shall demonstrate below.
Multivariate methods based on Granger causality
The testable definition of causality was introduced by Granger. Granger causality principle states that if some series Y(t) contains information in past terms that helps in the prediction of series X(t), then Y(t) is said to cause X(t). Granger causality principle can be expressed in terms of two-channel multivariateautoregressive model (MVAR). Granger in his later work
pointed out that the determination of causality is not possible when
the system of considered channels is not complete.
The measures based on Granger causality principle are: Granger Causality
Index (GCI), Directed Transfer Function (DTF) and Partial Directed
Coherence (PDC). These measures are defined in the framework of
Multivariate Autoregressive Model.
Multivariate Autoregressive Model
The AR model assumes that X(t)—a sample of data at a time t—can be expressed as a sum of p previous values of the samples from the set of k-signals weighted by model coefficients A plus a random value E(t):
(1)
The p is called the model order. For a k-channel process X(t) and E(t) are vectors of size k and the coefficients A are k×k-sized
matrices.
The model order may be determined by means of criteria developed in the
framework of information theory and the coefficients of the model are
found by means of the minimalization of the residual noise. In the
procedure correlation matrix between signals is calculated.
By the transformation to the frequency domain we get:
(2)
H(f) is a transfer matrix of the system, it contains
information about the relationships between signals and their spectral
characteristics. H(f) is non-symmetric, so it allows for finding causal dependencies.
Model order may be found by means of criteria developed in the framework of information theory, e.g. AIC criterion.
Granger Causality Index
Granger causality index showing the driving of channel x by channel y is defined as the logarithm of the ratio of residual variance for one channel to the residual variance of the two-channel model:
GCIy→x = ln (e/e1)
This definition can be extended to the multichannel system by
considering how the inclusion of the given channel changes the residual
variance ratios. To quantify directed influence from a channel xj to xi for n channel autoregressive process in time domain we consider n and n−1 dimensional MVAR models. First, the model is fitted to whole n-channel system, leading to the residual variance Vi,n(t) = var(Ei,n(t)) for signal xi. Next, a n−1 dimensional MVAR model is fitted for n−1 channels, excluding channel j, which leads to the residual variance Vi,n−1(t) = var (Ei,n−1(t)). Then Granger causality is defined as:
GCI is smaller or equal 1, since the variance of n-dimensional system is lower than the residual variance of a smaller, n−1 dimensional system.
GCI(t) estimates causality relations in time domain. For brain
signals the spectral characteristics of the signals is of interest,
because for a given task the increase of propagation in certain
frequency band may be accompanied by the decrease in another frequency
band. DTF or PDC are the estimators defined in the frequency domain.
Directed Transfer Function
Directed Transfer Function (DTF) was introduced by Kaminski and Blinowska in the form:
(3)
Where Hij(f) is an element of a transfer matrix of MVAR model.
DTF describes causal influence of channel j on channel i at frequency f. The above equation (3) defines a normalized version of DTF, which takes values from 0 to 1 producing a ratio between the inflow from channel j to channel i to all the inflows to channel i.
The non-normalized DTF which is directly related to the coupling strength is defined as:
(4)
DTF shows not only direct, but also cascade flows, namely in case of
propagation 1→2→3 it shows also propagation 1→3. In order to distinguish
direct from indirect flows direct Directed Transfer Function (dDTF) was
introduced.[25]
The dDTF is defined as a multiplication of a modified DTF by partial
coherence. The modification of DTF concerned normalization of the
function in such a way as to make the denominator independent of
frequency. The dDTFj→i showing direct propagation from channel j to i is defined as:
(5)
Where Cij(f) is partial coherence. The dDTFj→i has a nonzero value when both functions Fij(f) and Cij(f) are non-zero, in that case there exists a direct causal relation between channels j→i.
Distinguishing direct from indirect transmission is essential in case of
signals from implanted electrodes, for EEG signals recorded by scalp
electrodes it is not really important.
DTF may be used for estimation of propagation in case of point
processes e.g. spike trains or for the estimation of causal relations
between spike trains and Local Field Potentials.
Partial Directed Coherence
The partial directed coherence (PDC) was defined by Baccala and Sameshima in the following form:
(6)
In the above equation Aij(f) is an element of A(f)—a Fourier transform of MVAR model coefficients A(t), where aj(f) is j-th column of A(f)
and the asterisk denotes the transpose and complex conjugate operation.
Although it is a function operating in the frequency domain, the
dependence of A(f) on the frequency has not a direct
correspondence to the power spectrum. From normalization condition it
follows that PDC takes values from the interval [0,1]. PDC shows only
direct flows between channels. Unlike DTF, PDC is normalized to show a
ratio between the outflow from channel j to channel i to all the outflows from the source channel j,
so it emphasizes rather the sinks, not the sources. The normalization
of PDC affects the detected intensities of flow as was pointed out in.
Namely, adding further variables that are influenced by a source
variable decreases PDC, although the relationship between source and
target processes remains unchanged. In other words: the flow emitted in
one direction will be enhanced in comparison to the flows of the same
intensity emitted from a given source in several directions.
Time-varying estimators of effective connectivity
In
order to account for the dynamic changes of propagation, the method of
adaptive filtering or the method based on the sliding window may be
applied to estimators of connectivity. Both methods require multiple
repetition of the experiment to obtain statistically satisfactory
results and they produce similar results.
The adaptive methods, e.g. Kalman filtering, are more computationally
demanding, therefore methods based on sliding window may be recommended.
In the case of parametric model the number of data points kNT (k—number of channels, NT—number
of points in the data window) has to be bigger (preferably by order of
magnitude) than the number of parameters, which in case of MVAR is equal
to k2p (p—model order). In order to
evaluate dynamics of the process, a short data window has to be applied,
which requires an increase of the number of the data points, which may
be achieved by means of a repetition of the experiment. A non-stationary
recording may be divided into shorter time windows, short enough to
treat the data within a window as quasi-stationary. Estimation of MVAR
coefficients is based on calculation of the correlation matrix between
channels Rij of k signals Xi from multivariate set,
separately for each trial. The resulting model coefficients are based
on the correlation matrix averaged over trials. The correlation matrix
has the form:
(7)
The averaging concerns correlation matrices (model is fitted
independently for each short data window); the data are not averaged in
the process. The choice of window size is always a compromise between
quality of the fit and time resolution.
The errors of the SDTF may be evaluated by means of bootstrap method.
This procedure corresponds to simulations of other realizations of the
experiment. The variance of the function value is obtained by repeated
calculation of the results for a randomly selected (with repetitions)
pool of the original data trials.
Applications
The
estimation of brain connectivity has found numerous and notable
applications, namely when investigating brain changes associated with
the treatment of psychopathology like schizophrenia and depression, or following structural damage like in hemorrhage or tumor. The methods applied benefit from a parcellation approach, where regions of the brain are defined from atlases or DWI data, with connectivity metrics then extracted to compare changes within standardized regions.
Specifically, DTF found multiple applications, the early ones involved: localization of epileptic foci, estimation of EEG propagation in different sleep stages and wakefulness, determination of transmission between brain structures of an animal during a behavioral test.
One may observe the shifting of sources toward the front in
transition from wakefulness to the deeper sleep stages. In the deep
sleep the source is over corpus callosum, presumably it is connected with feeding the cortex from the sub-cortical structures.
One of the first applications of SDTF was determination of the
dynamic propagation during performance of finger movement and its
imagination,.
The results corresponded very well with the known phenomena of event
related synchronization and desynchronization such as decrease of the
activity in alpha and beta band and brief increase of activity in the
gamma band during movement in the areas corresponding to primary motor
cortex, beta rebound after movement and so-called surround effect.
Especially interesting was comparison of real finger movement and its
imagination. In case of real movement the short burst of gamma
propagation was observed from the electrode positioned over finger
primary motor cortex . In case of movement imagination this propagation
started later and a cross-talk between different sites overlying motor
area and supplementary motor area (SMA) was found. (The dynamics of propagation may be observed in animations).
Another applications of SDTF concerned evaluation of transmission
during cognitive experiments. The results of the Continuous Attention
Test (CAT) confirmed the engagement of prefrontal and frontal structures in the task and supported the hypothesis of an active inhibition by pre-SMA and right inferior frontal cortex. Animations of propagation during CAT test are available.
The results obtained by means of SDTF in experiments involving
working memory were compatible with fMRI studies on the localization of
the active sites and supplied the information concerning the temporal
interaction between them. The animation illustrating dynamics of the interaction are available.
Note that care should be taken to avoid spurious connectivity estimates when using EEG channel data. Recent articles highlight that previous claims
that DTF and PDC were insensitive to volume conduction were inaccurate.
Indeed, DTF results obtained for signals recorded from the scalp are in
general affected by volume conduction. Even though the effects of
volume conduction might be minimal in specific recording situations, appropriate preprocessing on channel data (such as source identification) should be performed before estimating DTF or PDC.
Conclusions
The
existence of well defined sources of brain activity connected with
particular experimental conditions are well established in fMRI
experiments, by means of inverse solution methods and intracortical
measurements. This kind of deterministic structure of brain activity
should affect functional connectivity, so reported in some works random
or barely distinguished from random connectivity structure may be
considered as a surprising phenomenon. This kind of results may be
explained by methodological errors: 1) unrobust methods of connectivity
estimation and, even more important, 2) application of bivariate
methods. When multivariate robust measures of connectivity are applied
for EEG analysis a clear picture of functional connectivity emerges.
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, it would be impossible for language, relationships, or personal identity to develop. Memory loss is usually described as forgetfulness or amnesia.
Memory is often understood as an informational processing system with explicit and implicit functioning that is made up of a sensory processor, short-term (or working) memory, and long-term memory. This can be related to the neuron.
The sensory processor allows information from the outside world to be
sensed in the form of chemical and physical stimuli and attended to
various levels of focus and intent. Working memory serves as an encoding
and retrieval processor. Information in the form of stimuli is encoded
in accordance with explicit or implicit functions by the working memory
processor. The working memory also retrieves information from previously
stored material. Finally, the function of long-term memory is to store
through various categorical models or systems.
Declarative, or explicit, memory is the conscious storage and recollection of data. Under declarative memory resides semantic and episodic memory. Semantic memory refers to memory that is encoded with specific meaning. Meanwhile, episodic memory refers to information that is encoded along a spatial and temporal plane. Declarative memory is usually the primary process thought of when referencing memory. Non-declarative, or implicit, memory is the unconscious storage and recollection of information. An example of a non-declarative process would be the unconscious learning or retrieval of information by way of procedural memory, or a priming phenomenon. Priming is the process of subliminally arousing specific responses from memory and shows that not all memory is consciously activated, whereas procedural memory is the slow and gradual learning of skills that often occurs without conscious attention to learning.
Memory is not a perfect processor, and is affected by many
factors. The ways by which information is encoded, stored, and retrieved
can all be corrupted. Pain, for example, has been identified as a
physical condition that impairs memory, and has been noted in animal
models as well as chronic pain patients. The amount of attention given new stimuli can diminish the amount of information that becomes encoded for storage.
Also, the storage process can become corrupted by physical damage to
areas of the brain that are associated with memory storage, such as the
hippocampus. Finally, the retrieval of information from long-term memory can be disrupted because of decay within long-term memory. Normal functioning, decay over time, and brain damage all affect the accuracy and capacity of the memory.
Sensory memory holds information, derived from the senses, less than
one second after an item is perceived. The ability to look at an item
and remember what it looked like with just a split second of
observation, or memorization, is an example of sensory memory. It is out
of cognitive control and is an automatic response. With very short
presentations, participants often report that they seem to "see" more
than they can actually report. The first precise experiments exploring
this form of sensory memory were conducted by George Sperling (1963)
using the "partial report paradigm." Subjects were presented with a
grid of 12 letters, arranged into three rows of four. After a brief
presentation, subjects were then played either a high, medium or low
tone, cuing them which of the rows to report. Based on these partial
report experiments, Sperling was able to show that the capacity of
sensory memory was approximately 12 items, but that it degraded very
quickly (within a few hundred milliseconds). Because this form of memory
degrades so quickly, participants would see the display but be unable
to report all of the items (12 in the "whole report" procedure) before
they decayed. This type of memory cannot be prolonged via rehearsal.
Three types of sensory memories exist. Iconic memory
is a fast decaying store of visual information, a type of sensory
memory that briefly stores an image that has been perceived for a small
duration. Echoic memory
is a fast decaying store of auditory information, also a sensory memory
that briefly stores sounds that have been perceived for short
durations. Haptic memory is a type of sensory memory that represents a database for touch stimuli.
Short-term memory, not to be confused with working memory, allows
recall for a period of several seconds to a minute without rehearsal.
Its capacity, however, is very limited. In 1956, George A. Miller (1920–2012), when working at Bell Laboratories, conducted experiments showing that the store of short-term memory was 7±2 items. (Hence, the title of his famous paper, "The Magical Number 7±2.") Modern perspectives estimate the capacity of short-term memory to be lower, typically on the order of 4–5 items, or argue for a more flexible limit based on information instead of items. Memory capacity can be increased through a process called chunking. For example, in recalling a ten-digit telephone number,
a person could chunk the digits into three groups: first, the area code
(such as 123), then a three-digit chunk (456), and, last, a four-digit
chunk (7890). This method of remembering telephone numbers is far more
effective than attempting to remember a string of 10 digits; this is
because we are able to chunk the information into meaningful groups of
numbers. This is reflected in some countries' tendencies to display
telephone numbers as several chunks of two to four numbers.
Short-term memory is believed to rely mostly on an acoustic code
for storing information, and to a lesser extent on a visual code. Conrad
(1964)
found that test subjects had more difficulty recalling collections of
letters that were acoustically similar, e.g., E, P, D. Confusion with
recalling acoustically similar letters rather than visually similar
letters implies that the letters were encoded acoustically. Conrad's
(1964) study, however, deals with the encoding of written text. Thus,
while the memory of written language may rely on acoustic components,
generalizations to all forms of memory cannot be made.
The storage in sensory memory and short-term memory generally has a
strictly limited capacity and duration. This means that information is
not retained indefinitely. By contrast, while the total capacity of
long-term memory has yet to be established, it can store much larger
quantities of information. Furthermore, it can store this information
for a much longer duration, potentially for a whole life span. For
example, given a random seven-digit number, one may remember it for only
a few seconds before forgetting, suggesting it was stored in short-term
memory. On the other hand, one can remember telephone numbers for many
years through repetition; this information is said to be stored in
long-term memory.
While short-term memory encodes information acoustically, long-term memory encodes it semantically: Baddeley (1966)
discovered that, after 20 minutes, test subjects had the most
difficulty recalling a collection of words that had similar meanings
(e.g. big, large, great, huge) long-term. Another part of long-term
memory is episodic memory, "which attempts to capture information such
as 'what', 'when' and 'where'". With episodic memory, individuals are able to recall specific events such as birthday parties and weddings.
Short-term memory is supported by transient patterns of neuronal communication, dependent on regions of the frontal lobe (especially dorsolateral prefrontal cortex) and the parietal lobe.
Long-term memory, on the other hand, is maintained by more stable and
permanent changes in neural connections widely spread throughout the
brain. The hippocampus
is essential (for learning new information) to the consolidation of
information from short-term to long-term memory, although it does not
seem to store information itself. It was thought that without the
hippocampus new memories were unable to be stored into long-term memory
and that there would be a very short attention span, as first gleaned from patient Henry Molaison
after what was thought to be the full removal of both his hippocampi.
More recent examination of his brain, post-mortem, shows that the
hippocampus was more intact than first thought, throwing theories drawn
from the initial data into question. The hippocampus may be involved in
changing neural connections for a period of three months or more after
the initial learning.
Research has suggested that long-term memory storage in humans may be maintained by DNA methylation, and the 'prion' gene.
Further research investigated the molecular basis for long-term memory. By 2015 it had become clear that long-term memory requires gene transcription activation and de novo protein synthesis.
Long-term memory formation depends on both the activation of memory
promoting genes and the inhibition of memory suppressor genes, and DNA methylation/DNA demethylation was found to be a major mechanism for achieving this dual regulation.
Rats with a new, strong long-term memory due to contextual fear conditioning
have reduced expression of about 1,000 genes and increased expression
of about 500 genes in the hippocampus 24 hours after training, thus
exhibiting modified expression of 9.17% of the rat hippocampal genome.
Reduced gene expressions were associated with methylations of those
genes.
Considerable further research into long-term memory has
illuminated the molecular mechanisms by which methylations are
established or removed, as reviewed in 2022. These mechanisms include, for instance, signal-responsive TOP2B-induced double-strand breaks in immediate early genes. Also the messenger RNAs of many genes that had been subjected to methylation-controlled increases or decreases are transported by neural granules (messenger RNP) to the dendritic spines. At these locations the messenger RNAs can be translated into the proteins that control signaling at neuronalsynapses.
The multi-store model has been criticised for being too
simplistic. For instance, long-term memory is believed to be actually
made up of multiple subcomponents, such as episodic and procedural memory.
It also proposes that rehearsal is the only mechanism by which
information eventually reaches long-term storage, but evidence shows us
capable of remembering things without rehearsal.
The model also shows all the memory stores as being a single unit
whereas research into this shows differently. For example, short-term
memory can be broken up into different units such as visual information
and acoustic information. In a study by Zlonoga and Gerber (1986),
patient 'KF' demonstrated certain deviations from the Atkinson–Shiffrin
model. Patient KF was brain damaged,
displaying difficulties regarding short-term memory. Recognition of
sounds such as spoken numbers, letters, words, and easily identifiable
noises (such as doorbells and cats meowing) were all impacted. Visual
short-term memory was unaffected, suggesting a dichotomy between visual
and audial memory.
In 1974 Baddeley and Hitch proposed a "working memory model" that
replaced the general concept of short-term memory with active
maintenance of information in short-term storage. In this model, working
memory consists of three basic stores: the central executive, the
phonological loop, and the visuo-spatial sketchpad. In 2000 this model
was expanded with the multimodal episodic buffer (Baddeley's model of working memory).
The central executive essentially acts as an attention sensory
store. It channels information to the three component processes: the
phonological loop, the visuospatial sketchpad, and the episodic buffer.
The phonological loop stores auditory information by silently
rehearsing sounds or words in a continuous loop: the articulatory
process (for example the repetition of a telephone number over and over
again). A short list of data is easier to remember. The phonological
loop is occasionally disrupted. Irrelevant speech or background noise can impede the phonological loop. Articulatory suppression
can also confuse encoding and words that sound similar can be switched
or misremembered through the phonological similarity effect. the
phonological loop also has a limit to how much it can hold at once which
means that it is easier to remember a lot of short words rather than a
lot of long words, according to the word length effect.
The visuospatial sketchpad
stores visual and spatial information. It is engaged when performing
spatial tasks (such as judging distances) or visual ones (such as
counting the windows on a house or imagining images). Those with aphantasia will not be able to engage the visuospatial sketchpad.
The episodic buffer is dedicated to linking information across
domains to form integrated units of visual, spatial, and verbal
information and chronological ordering (e.g., the memory of a story or a
movie scene). The episodic buffer is also assumed to have links to
long-term memory and semantic meaning.
The working memory model explains many practical observations,
such as why it is easier to do two different tasks, one verbal and one
visual, than two similar tasks, and the aforementioned word-length
effect. Working memory is also the premise for what allows us to do
everyday activities involving thought. It is the section of memory where
we carry out thought processes and use them to learn and reason about
topics.
Types
Researchers distinguish between recognition and recall
memory. Recognition memory tasks require individuals to indicate
whether they have encountered a stimulus (such as a picture or a word)
before. Recall memory tasks require participants to retrieve previously
learned information. For example, individuals might be asked to produce a
series of actions they have seen before or to say a list of words they
have heard before.
By information type
Topographical memory involves the ability to orient oneself in space, to recognize and follow an itinerary, or to recognize familiar places. Getting lost when traveling alone is an example of the failure of topographic memory.
Declarative memory requires conscious recall, in that some conscious process must call back the information. It is sometimes called explicit memory, since it consists of information that is explicitly stored and retrieved. Declarative memory can be further sub-divided into semantic memory, concerning principles and facts taken independent of context; and episodic memory,
concerning information specific to a particular context, such as a time
and place. Semantic memory allows the encoding of abstract knowledge
about the world, such as "Paris is the capital of France". Episodic
memory, on the other hand, is used for more personal memories, such as
the sensations, emotions, and personal associations
of a particular place or time. Episodic memories often reflect the
"firsts" in life such as a first kiss, first day of school or first time
winning a championship. These are key events in one's life that can be
remembered clearly.
Research suggests that declarative memory is supported by several
functions of the medial temporal lobe system which includes the
hippocampus. Autobiographical memory
– memory for particular events within one's own life – is generally
viewed as either equivalent to, or a subset of, episodic memory. Visual memory
is part of memory preserving some characteristics of our senses
pertaining to visual experience. One is able to place in memory
information that resembles objects, places, animals or people in sort of
a mental image. Visual memory can result in priming and it is assumed some kind of perceptual representational system underlies this phenomenon.
Procedural
In contrast, procedural memory (or implicit memory) is not based on the conscious recall of information, but on implicit learning. It can best be summarized as remembering how to do something. Procedural memory is primarily used in learning motor skills
and can be considered a subset of implicit memory. It is revealed when
one does better in a given task due only to repetition – no new explicit
memories have been formed, but one is unconsciously accessing aspects of those previous experiences. Procedural memory involved in motor learning depends on the cerebellum and basal ganglia.
A characteristic of procedural memory is that the things
remembered are automatically translated into actions, and thus sometimes
difficult to describe. Some examples of procedural memory include the
ability to ride a bike or tie shoelaces.
By temporal direction
Another major way to distinguish different memory functions is whether the content to be remembered is in the past, retrospective memory, or in the future, prospective memory. John Meacham introduced this distinction in a paper presented at the 1975 American Psychological Association annual meeting and subsequently included by Ulric Neisser in his 1982 edited volume, Memory Observed: Remembering in Natural Contexts.
Thus, retrospective memory as a category includes semantic, episodic
and autobiographical memory. In contrast, prospective memory is memory
for future intentions, or remembering to remember (Winograd,
1988). Prospective memory can be further broken down into event- and
time-based prospective remembering. Time-based prospective memories are
triggered by a time-cue, such as going to the doctor (action) at 4pm
(cue). Event-based prospective memories are intentions triggered by
cues, such as remembering to post a letter (action) after seeing a
mailbox (cue). Cues do not need to be related to the action (as the
mailbox/letter example), and lists, sticky-notes, knotted handkerchiefs,
or string around the finger all exemplify cues that people use as
strategies to enhance prospective memory.
Study techniques
To assess infants
Infants
do not have the language ability to report on their memories and so
verbal reports cannot be used to assess very young children's memory.
Throughout the years, however, researchers have adapted and developed a
number of measures for assessing both infants' recognition memory and
their recall memory. Habituation and operant conditioning
techniques have been used to assess infants' recognition memory and the
deferred and elicited imitation techniques have been used to assess
infants' recall memory.
Techniques used to assess infants' recognition memory include the following:
Visual paired comparison procedure (relies on habituation):
infants are first presented with pairs of visual stimuli, such as two
black-and-white photos of human faces, for a fixed amount of time; then,
after being familiarized with the two photos, they are presented with
the "familiar" photo and a new photo. The time spent looking at each
photo is recorded. Looking longer at the new photo indicates that they
remember the "familiar" one. Studies using this procedure have found
that 5- to 6-month-olds can retain information for as long as fourteen
days.
Operant conditioning technique: infants are placed in a crib
and a ribbon that is connected to a mobile overhead is tied to one of
their feet. Infants notice that when they kick their foot the mobile
moves – the rate of kicking increases dramatically within minutes.
Studies using this technique have revealed that infants' memory
substantially improves over the first 18-months. Whereas 2- to
3-month-olds can retain an operant response (such as activating the
mobile by kicking their foot) for a week, 6-month-olds can retain it for
two weeks, and 18-month-olds can retain a similar operant response for
as long as 13 weeks.
Techniques used to assess infants' recall memory include the following:
Deferred imitation technique: an experimenter shows
infants a unique sequence of actions (such as using a stick to push a
button on a box) and then, after a delay, asks the infants to imitate
the actions. Studies using deferred imitation have shown that
14-month-olds' memories for the sequence of actions can last for as long
as four months.
Elicited imitation technique: is very similar to the deferred
imitation technique; the difference is that infants are allowed to
imitate the actions before the delay. Studies using the elicited
imitation technique have shown that 20-month-olds can recall the action
sequences twelve months later.
To assess children and older adults
Researchers use a variety of tasks to assess older children and adults' memory. Some examples are:
Paired associate learning – when one learns to associate
one specific word with another. For example, when given a word such as
"safe" one must learn to say another specific word, such as "green".
This is stimulus and response.
Free recall – during this task a subject would be asked to
study a list of words and then later they will be asked to recall or
write down as many words that they can remember, similar to free
response questions.
Earlier items are affected by retroactive interference (RI), which
means the longer the list, the greater the interference, and the less
likelihood that they are recalled. On the other hand, items that have
been presented lastly suffer little RI, but suffer a great deal from
proactive interference (PI), which means the longer the delay in recall,
the more likely that the items will be lost.
Cued recall – one is given a significant hints to help
retrieve information that has been previously encoded into the person's
memory; typically this can involve a word relating to the information
being asked to remember. This is similar to fill in the blank assessments used in classrooms.
Recognition – subjects are asked to remember a list of words
or pictures, after which point they are asked to identify the previously
presented words or pictures from among a list of alternatives that were
not presented in the original list. This is similar to multiple choice assessments.
Detection paradigm – individuals are shown a number of
objects and color samples during a certain period of time. They are then
tested on their visual ability to remember as much as they can by
looking at testers and pointing out whether the testers are similar to
the sample, or if any change is present.
Savings method – compares the speed of originally learning to the speed of relearning it. The amount of time saved measures memory.
Implicit-memory tasks – information is drawn from memory without conscious realization.
Transience – memories degrade with the passing of time.
This occurs in the storage stage of memory, after the information has
been stored and before it is retrieved. This can happen in sensory,
short-term, and long-term storage. It follows a general pattern where
the information is rapidly forgotten during the first couple of days or
years, followed by small losses in later days or years.
Absent-mindedness – Memory failure due to the lack of attention.
Attention plays a key role in storing information into long-term
memory; without proper attention, the information might not be stored,
making it impossible to be retrieved later.
Damage to certain areas in patients and animal models and
subsequent memory deficits is a primary source of information. However,
rather than implicating a specific area, it could be that damage to
adjacent areas, or to a pathway traveling through the area is
actually responsible for the observed deficit. Further, it is not
sufficient to describe memory, and its counterpart, learning, as solely dependent on specific brain regions. Learning and memory are usually attributed to changes in neuronal synapses, thought to be mediated by long-term potentiation and long-term depression.
In general, the more emotionally charged an event or experience
is, the better it is remembered; this phenomenon is known as the memory enhancement effect. Patients with amygdala damage, however, do not show a memory enhancement effect.
Hebb
distinguished between short-term and long-term memory. He postulated
that any memory that stayed in short-term storage for a long enough time
would be consolidated into a long-term memory. Later research showed
this to be false. Research has shown that direct injections of cortisol or epinephrine
help the storage of recent experiences. This is also true for
stimulation of the amygdala. This proves that excitement enhances memory
by the stimulation of hormones that affect the amygdala. Excessive or
prolonged stress (with prolonged cortisol) may hurt memory storage.
Patients with amygdalar damage are no more likely to remember
emotionally charged words than nonemotionally charged ones. The
hippocampus is important for explicit memory. The hippocampus is also
important for memory consolidation. The hippocampus receives input from
different parts of the cortex and sends its output out to different
parts of the brain also. The input comes from secondary and tertiary
sensory areas that have processed the information a lot already.
Hippocampal damage may also cause memory loss and problems with memory storage. This memory loss includes retrograde amnesia which is the loss of memory for events that occurred shortly before the time of brain damage.
Cognitive neuroscience
Cognitive
neuroscientists consider memory as the retention, reactivation, and
reconstruction of the experience-independent internal representation.
The term of internal representation
implies that such a definition of memory contains two components: the
expression of memory at the behavioral or conscious level, and the
underpinning physical neural changes (Dudai 2007). The latter component
is also called engram
or memory traces (Semon 1904). Some neuroscientists and psychologists
mistakenly equate the concept of engram and memory, broadly conceiving
all persisting after-effects of experiences as memory; others argue
against this notion that memory does not exist until it is revealed in
behavior or thought (Moscovitch 2007).
One question that is crucial in cognitive neuroscience is how
information and mental experiences are coded and represented in the
brain. Scientists have gained much knowledge about the neuronal codes
from the studies of plasticity, but most of such research has been
focused on simple learning in simple neuronal circuits; it is
considerably less clear about the neuronal changes involved in more
complex examples of memory, particularly declarative memory that
requires the storage of facts and events (Byrne 2007). Convergence-divergence zones
might be the neural networks where memories are stored and retrieved.
Considering that there are several kinds of memory, depending on types
of represented knowledge, underlying mechanisms, processes functions and
modes of acquisition, it is likely that different brain areas support
different memory systems and that they are in mutual relationships in
neuronal networks: "components of memory representation are distributed
widely across different parts of the brain as mediated by multiple
neocortical circuits".
Encoding. Encoding of working memory
involves the spiking of individual neurons induced by sensory input,
which persists even after the sensory input disappears (Jensen and
Lisman 2005; Fransen et al. 2002). Encoding of episodic memory involves persistent changes in molecular structures that alter synaptic transmission between neurons. Examples of such structural changes include long-term potentiation (LTP) or spike-timing-dependent plasticity
(STDP). The persistent spiking in working memory can enhance the
synaptic and cellular changes in the encoding of episodic memory (Jensen
and Lisman 2005).
Working memory. Recent functional imaging studies detected working memory signals in both medial temporal lobe (MTL), a brain area strongly associated with long-term memory, and prefrontal cortex
(Ranganath et al. 2005), suggesting a strong relationship between
working memory and long-term memory. However, the substantially more
working memory signals seen in the prefrontal lobe suggest that this
area plays a more important role in working memory than MTL (Suzuki
2007).
Consolidation and reconsolidation. Short-term memory
(STM) is temporary and subject to disruption, while long-term memory
(LTM), once consolidated, is persistent and stable. Consolidation of STM
into LTM at the molecular level presumably involves two processes:
synaptic consolidation and system consolidation. The former involves a
protein synthesis process in the medial temporal lobe (MTL), whereas the
latter transforms the MTL-dependent memory into an MTL-independent
memory over months to years (Ledoux 2007). In recent years, such
traditional consolidation dogma has been re-evaluated as a result of the
studies on reconsolidation. These studies showed that prevention after retrieval
affects subsequent retrieval of the memory (Sara 2000). New studies
have shown that post-retrieval treatment with protein synthesis
inhibitors and many other compounds can lead to an amnestic state (Nadel
et al. 2000b; Alberini 2005; Dudai 2006). These findings on
reconsolidation fit with the behavioral evidence that retrieved memory
is not a carbon copy of the initial experiences, and memories are
updated during retrieval.
Study of the genetics of human memory is in its infancy though many
genes have been investigated for their association to memory in humans
and non-human animals. A notable initial success was the association of APOE with memory dysfunction in Alzheimer's disease.
The search for genes associated with normally varying memory continues.
One of the first candidates for normal variation in memory is the
protein KIBRA,
which appears to be associated with the rate at which material is
forgotten over a delay period. There has been some evidence that
memories are stored in the nucleus of neurons.
Genetic underpinnings
Several genes,
proteins and enzymes have been extensively researched for their
association with memory. Long-term memory, unlike short-term memory, is
dependent upon the synthesis of new proteins.
This occurs within the cellular body, and concerns the particular
transmitters, receptors, and new synapse pathways that reinforce the
communicative strength between neurons. The production of new proteins
devoted to synapse reinforcement is triggered after the release of
certain signaling substances (such as calcium within hippocampal
neurons) in the cell. In the case of hippocampal cells, this release is
dependent upon the expulsion of magnesium (a binding molecule) that is
expelled after significant and repetitive synaptic signaling. The
temporary expulsion of magnesium frees NMDA receptors to release calcium
in the cell, a signal that leads to gene transcription and the
construction of reinforcing proteins. For more information, see long-term potentiation (LTP).
One of the newly synthesized proteins in LTP is also critical for
maintaining long-term memory. This protein is an autonomously active
form of the enzyme protein kinase C (PKC), known as PKMζ.
PKMζ maintains the activity-dependent enhancement of synaptic strength
and inhibiting PKMζ erases established long-term memories, without
affecting short-term memory or, once the inhibitor is eliminated, the
ability to encode and store new long-term memories is restored. Also, BDNF is important for the persistence of long-term memories.
The long-term stabilization of synaptic changes is also
determined by a parallel increase of pre- and postsynaptic structures
such as axonal bouton, dendritic spine and postsynaptic density.
On the molecular level, an increase of the postsynaptic scaffolding proteins PSD-95 and HOMER1c has been shown to correlate with the stabilization of synaptic enlargement. The cAMP response element-binding protein (CREB) is a transcription factor
which is believed to be important in consolidating short-term to
long-term memories, and which is believed to be downregulated in
Alzheimer's disease.
DNA methylation and demethylation
Rats exposed to an intense learning
event may retain a life-long memory of the event, even after a single
training session. The long-term memory of such an event appears to be
initially stored in the hippocampus, but this storage is transient. Much of the long-term storage of the memory seems to take place in the anterior cingulate cortex.
When such an exposure was experimentally applied, more than 5,000
differently methylated DNA regions appeared in the hippocampus neuronal genome of the rats at one and at 24 hours after training.e alterations in methylation pattern occurred at many genes that were downregulated, often due to the formation of new 5-methylcytosine
sites in CpG rich regions of the genome. Furthermore, many other genes
were upregulated, likely often due to hypomethylation. Hypomethylation
often results from the removal of methyl groups from previously existing
5-methylcytosines in DNA. Demethylation is carried out by several
proteins acting in concert, including the TET enzymes as well as enzymes of the DNA base excision repair pathway (see Epigenetics in learning and memory).
The pattern of induced and repressed genes in brain neurons subsequent
to an intense learning event likely provides the molecular basis for a
long-term memory of the event.
Studies of the molecular basis for memory formation indicate that epigenetic mechanisms operating in neurons in the brain play a central role in determining this capability. Key epigenetic mechanisms involved in memory include the methylation and demethylation of neuronal DNA, as well as modifications of histone proteins including methylations, acetylations and deacetylations.
Stimulation of brain activity in memory formation is often accompanied by the generation of damage in neuronal DNA that is followed by repair associated with persistent epigenetic alterations. In particular the DNA repair processes of non-homologous end joining and base excision repair are employed in memory formation.
DNA topoisomerase 2-beta in learning and memory
During a new learning experience, a set of genes is rapidly expressed in the brain. This induced gene expression is considered to be essential for processing the information being learned. Such genes are referred to as immediate early genes (IEGs). DNA topoisomerase 2-beta (TOP2B) activity is essential for the expression of IEGs in a type of learning experience in mice termed associative fear memory. Such a learning experience appears to rapidly trigger TOP2B to induce double-strand breaks in the promoter DNA of IEG genes that function in neuroplasticity. Repair
of these induced breaks is associated with DNA demethylation of IEG
gene promoters allowing immediate expression of these IEG genes.
Regulatory
sequence in a promoter at a transcription start site with a paused RNA
polymerase and a TOP2B-induced double-strand break
The double-strand breaks that are induced during a learning
experience are not immediately repaired. About 600 regulatory sequences
in promoters and about 800 regulatory sequences in enhancers appear to depend on double strand breaks initiated by topoisomerase 2-beta (TOP2B) for activation.
The induction of particular double-strand breaks are specific with
respect to their inducing signal. When neurons are activated in vitro, just 22 of TOP2B-induced double-strand breaks occur in their genomes.
Such TOP2B-induced double-strand breaks are accompanied by at least four enzymes of the non-homologous end joining (NHEJ) DNA repair pathway
(DNA-PKcs, KU70, KU80, and DNA LIGASE IV) (see Figure). These enzymes
repair the double-strand breaks within about 15 minutes to two hours.
The double-strand breaks in the promoter are thus associated with TOP2B
and at least these four repair enzymes. These proteins are present
simultaneously on a single promoter nucleosome
(there are about 147 nucleotides in the DNA sequence wrapped around a
single nucleosome) located near the transcription start site of their
target gene.
Brain regions involved in memory formation including medial prefrontal cortex (mPFC)
The double-strand break introduced by TOP2B apparently frees the part of the promoter at an RNA polymerase-bound transcription start site to physically move to its associated enhancer (see regulatory sequence). This allows the enhancer, with its bound transcription factors and mediator proteins, to directly interact with the RNA polymerase paused at the transcription start site to start transcription.
Contextual fear conditioning
in the mouse causes the mouse to have a long-term memory and fear of
the location in which it occurred. Contextual fear conditioning causes
hundreds of DSBs in mouse brain medial prefrontal cortex (mPFC) and
hippocampus neurons (see Figure: Brain regions involved in memory
formation). These DSBs predominately activate genes involved in synaptic
processes, that are important for learning and memory.
Chemistry of Memory : Molecular basis of thought storage and memory formation
A
considerable amount of research is underway on the molecular basis of
thought storage, memory consolidation and formation of logical thought
processes.In 2001 it has been proposed that the folding of glycoproteins
by intermolecular or intramolecular hydrogen bonding may be the key
process involved in memory storage.
The hydrogen bonding protein patterns hypothesis (HBPPH) proposes the
formation of hydrogen bonds between hydroxyl groups of sugar moieties
present in the glycoproteins with hydroxyl (or NH) groups of other sugar
moieties or biomolecules that can lead to the creation of certain
partly folded protein patterns. This provides a reasonable mechanism by
which the brain may be able to gather and store information by the
construction of intermolecular and intramolecular networks of folded
glycoproteins. Support for partly folded proteins being involved in memory processes has come from recent researches in the field.
In infancy
For the inability of adults to retrieve early memories, see Childhood amnesia.
Up until the mid-1980s it was assumed that infants could not encode, retain, and retrieve information. A growing body of research now indicates that infants as young as 6-months can recall information after a 24-hour delay.
Furthermore, research has revealed that as infants grow older they can
store information for longer periods of time; 6-month-olds can recall
information after a 24-hour period, 9-month-olds after up to five weeks,
and 20-month-olds after as long as twelve months.
In addition, studies have shown that with age, infants can store
information faster. Whereas 14-month-olds can recall a three-step
sequence after being exposed to it once, 6-month-olds need approximately
six exposures in order to be able to remember it.
Although 6-month-olds can recall information over the short-term,
they have difficulty recalling the temporal order of information. It is
only by 9 months of age that infants can recall the actions of a
two-step sequence in the correct temporal order – that is, recalling
step 1 and then step 2. In other words, when asked to imitate a two-step action sequence (such
as putting a toy car in the base and pushing in the plunger to make the
toy roll to the other end), 9-month-olds tend to imitate the actions of
the sequence in the correct order (step 1 and then step 2). Younger
infants (6-month-olds) can only recall one step of a two-step sequence. Researchers have suggested that these age differences are probably due to the fact that the dentate gyrus of the hippocampus and the frontal components of the neural network are not fully developed at the age of 6-months.
In fact, the term 'infantile amnesia' refers to the phenomenon of
accelerated forgetting during infancy. Importantly, infantile amnesia
is not unique to humans, and preclinical research (using rodent models)
provides insight into the precise neurobiology of this phenomenon. A
review of the literature from behavioral neuroscientist Jee Hyun Kim suggests that accelerated forgetting during early life is at least partly due to rapid growth of the brain during this period.
One of the key concerns of older adults is the experience of memory loss, especially as it is one of the hallmark symptoms of Alzheimer's disease. However, memory loss is qualitatively different in normal aging
from the kind of memory loss associated with a diagnosis of Alzheimer's
(Budson & Price, 2005). Research has revealed that individuals'
performance on memory tasks that rely on frontal regions declines with
age. Older adults tend to exhibit deficits on tasks that involve knowing
the temporal order in which they learned information; source memory tasks that require them to remember the specific circumstances or context in which they learned information;
and prospective memory tasks that involve remembering to perform an act
at a future time. Older adults can manage their problems with
prospective memory by using appointment books, for example.
Gene transcription profiles were determined for the human frontal cortex
of individuals from age 26 to 106 years. Numerous genes were identified
with reduced expression after age 40, and especially after age 70. Genes that play central roles in memory and learning were among those showing the most significant reduction with age. There was also a marked increase in DNA damage, likely oxidative damage, in the promoters
of those genes with reduced expression. It was suggested that DNA
damage may reduce the expression of selectively vulnerable genes
involved in memory and learning.
Much of the current knowledge of memory has come from studying memory disorders, particularly loss of memory, known as amnesia.
Amnesia can result from extensive damage to: (a) the regions of the
medial temporal lobe, such as the hippocampus, dentate gyrus, subiculum,
amygdala, the parahippocampal, entorhinal, and perirhinal cortices
or the (b) midline diencephalic region, specifically the dorsomedial
nucleus of the thalamus and the mammillary bodies of the hypothalamus.
There are many sorts of amnesia, and by studying their different forms,
it has become possible to observe apparent defects in individual
sub-systems of the brain's memory systems, and thus hypothesize their
function in the normally working brain. Other neurological disorders such as Alzheimer's disease and Parkinson's disease can also affect memory and cognition.
Hyperthymesia,
or hyperthymesic syndrome, is a disorder that affects an individual's
autobiographical memory, essentially meaning that they cannot forget
small details that otherwise would not be stored. Korsakoff's syndrome,
also known as Korsakoff's psychosis, amnesic-confabulatory syndrome, is
an organic brain disease that adversely affects memory by widespread
loss or shrinkage of neurons within the prefrontal cortex.
While not a disorder, a common temporary failure of word retrieval from memory is the tip-of-the-tongue phenomenon. Those with anomic aphasia
(also called nominal aphasia or Anomia), however, do experience the
tip-of-the-tongue phenomenon on an ongoing basis due to damage to the
frontal and parietal lobes of the brain.
Interference can hamper memorization and retrieval. There is retroactive interference, when learning new information makes it harder to recall old information and proactive interference,
where prior learning disrupts recall of new information. Although
interference can lead to forgetting, it is important to keep in mind
that there are situations when old information can facilitate learning
of new information. Knowing Latin, for instance, can help an individual
learn a related language such as French – this phenomenon is known as
positive transfer.
Stress has a significant effect on memory formation and learning. In
response to stressful situations, the brain releases hormones and
neurotransmitters (ex. glucocorticoids and catecholamines) which affect
memory encoding processes in the hippocampus. Behavioural research on
animals shows that chronic stress produces adrenal hormones which impact
the hippocampal structure in the brains of rats.
An experimental study by German cognitive psychologists L. Schwabe and
O. Wolf demonstrates how learning under stress also decreases memory
recall in humans.
In this study, 48 healthy female and male university students
participated in either a stress test or a control group. Those randomly
assigned to the stress test group had a hand immersed in ice cold water
(the reputable SECPT or 'Socially Evaluated Cold Pressor Test') for up
to three minutes, while being monitored and videotaped. Both the stress
and control groups were then presented with 32 words to memorize.
Twenty-four hours later, both groups were tested to see how many words
they could remember (free recall) as well as how many they could
recognize from a larger list of words (recognition performance). The
results showed a clear impairment of memory performance in the stress
test group, who recalled 30% fewer words than the control group. The
researchers suggest that stress experienced during learning distracts
people by diverting their attention during the memory encoding process.
However, memory performance can be enhanced when material is
linked to the learning context, even when learning occurs under stress. A
separate study by cognitive psychologists Schwabe and Wolf shows that
when retention testing is done in a context similar to or congruent with
the original learning task (i.e., in the same room), memory impairment
and the detrimental effects of stress on learning can be attenuated. Seventy-two healthy female and male university students, randomly assigned to the SECPT stress test
or to a control group, were asked to remember the locations of 15 pairs
of picture cards – a computerized version of the card game
"Concentration" or "Memory". The room in which the experiment took place
was infused with the scent of vanilla, as odour is a strong cue for
memory. Retention testing took place the following day, either in the
same room with the vanilla scent again present, or in a different room
without the fragrance. The memory performance of subjects who
experienced stress during the object-location task decreased
significantly when they were tested in an unfamiliar room without the
vanilla scent (an incongruent context); however, the memory performance
of stressed subjects showed no impairment when they were tested in the
original room with the vanilla scent (a congruent context). All
participants in the experiment, both stressed and unstressed, performed
faster when the learning and retrieval contexts were similar.
This research on the effects of stress on memory may have practical implications for education, for eyewitness testimony
and for psychotherapy: students may perform better when tested in their
regular classroom rather than an exam room, eyewitnesses may recall
details better at the scene of an event than in a courtroom, and persons
with post-traumatic stress may improve when helped to situate their memories of a traumatic event in an appropriate context.
Stressful life experiences may be a cause of memory loss as a person ages. Glucocorticoids that are released during stress cause damage to neurons that are located in the hippocampal
region of the brain. Therefore, the more stressful situations that
someone encounters, the more susceptible they are to memory loss later
on. The CA1 neurons found in the hippocampus are destroyed due to glucocorticoids decreasing the release of glucose and the reuptake of glutamate. This high level of extracellular glutamate allows calcium to enter NMDA receptors
which in return kills neurons. Stressful life experiences can also
cause repression of memories where a person moves an unbearable memory
to the unconscious mind. This directly relates to traumatic events in one's past such as kidnappings, being prisoners of war or sexual abuse as a child.
The more long term the exposure to stress is, the more impact it
may have. However, short term exposure to stress also causes impairment
in memory by interfering with the function of the hippocampus. Research
shows that subjects placed in a stressful situation for a short amount
of time still have blood glucocorticoid levels that have increased
drastically when measured after the exposure is completed. When subjects
are asked to complete a learning task after short term exposure they
often have difficulties. Prenatal stress also hinders the ability to
learn and memorize by disrupting the development of the hippocampus and
can lead to unestablished long term potentiation in the offspring of
severely stressed parents. Although the stress is applied prenatally,
the offspring show increased levels of glucocorticoids when they are
subjected to stress later on in life.
One explanation for why children from lower socioeconomic backgrounds
tend to display poorer memory performance than their higher-income peers
is the effects of stress accumulated over the course of the lifetime.
The effects of low income on the developing hippocampus is also thought
be mediated by chronic stress responses which may explain why children
from lower and higher-income backgrounds differ in terms of memory
performance.
Sleep affects memory consolidation. During sleep, the neural
connections in the brain are strengthened. This enhances the brain's
abilities to stabilize and retain memories. There have been several
studies which show that sleep improves the retention of memory, as
memories are enhanced through active consolidation. System consolidation
takes place during slow-wave sleep (SWS).
This process implicates that memories are reactivated during sleep, but
that the process does not enhance every memory. It also implicates that
qualitative changes are made to the memories when they are transferred
to long-term store during sleep. During sleep, the hippocampus replays
the events of the day for the neocortex. The neocortex then reviews and
processes memories, which moves them into long-term memory. When one
does not get enough sleep it makes it more difficult to learn as these
neural connections are not as strong, resulting in a lower retention
rate of memories. Sleep deprivation makes it harder to focus, resulting
in inefficient learning.
Furthermore, some studies have shown that sleep deprivation can lead to
false memories as the memories are not properly transferred to
long-term memory.
One of the primary functions of sleep is thought to be the improvement
of the consolidation of information, as several studies have
demonstrated that memory depends on getting sufficient sleep between
training and test.
Additionally, data obtained from neuroimaging studies have shown
activation patterns in the sleeping brain that mirror those recorded
during the learning of tasks from the previous day, suggesting that new memories may be solidified through such rehearsal.[128]
Construction for general manipulation
Although
people often think that memory operates like recording equipment, this
is not the case. The molecular mechanisms underlying the induction and
maintenance of memory are very dynamic and comprise distinct phases
covering a time window from seconds to even a lifetime.
In fact, research has revealed that our memories are constructed:
"current hypotheses suggest that constructive processes allow
individuals to simulate and imagine future episodes,
happenings, and scenarios. Since the future is not an exact repetition
of the past, simulation of future episodes requires a complex system
that can draw on the past in a manner that flexibly extracts and
recombines elements of previous experiences – a constructive rather than
a reproductive system."
People can construct their memories when they encode them and/or when
they recall them. To illustrate, consider a classic study conducted by
Elizabeth Loftus and John Palmer (1974)
in which people were instructed to watch a film of a traffic accident
and then asked about what they saw. The researchers found that the
people who were asked, "How fast were the cars going when they smashed into each other?" gave higher estimates than those who were asked, "How fast were the cars going when they hit
each other?" Furthermore, when asked a week later whether they had seen
broken glass in the film, those who had been asked the question with smashed were twice more likely to report that they had seen broken glass than those who had been asked the question with hit
(there was no broken glass depicted in the film). Thus, the wording of
the questions distorted viewers' memories of the event. Importantly, the
wording of the question led people to construct different memories of
the event – those who were asked the question with smashed
recalled a more serious car accident than they had actually seen. The
findings of this experiment were replicated around the world, and
researchers consistently demonstrated that when people were provided
with misleading information they tended to misremember, a phenomenon
known as the misinformation effect.
Research has revealed that asking individuals to repeatedly
imagine actions that they have never performed or events that they have
never experienced could result in false memories. For instance, Goff and
Roediger
(1998) asked participants to imagine that they performed an act (e.g.,
break a toothpick) and then later asked them whether they had done such a
thing. Findings revealed that those participants who repeatedly
imagined performing such an act were more likely to think that they had
actually performed that act during the first session of the experiment.
Similarly, Garry and her colleagues (1996)
asked college students to report how certain they were that they
experienced a number of events as children (e.g., broke a window with
their hand) and then two weeks later asked them to imagine four of those
events. The researchers found that one-fourth of the students asked to
imagine the four events reported that they had actually experienced such
events as children. That is, when asked to imagine the events they were
more confident that they experienced the events.
Research reported in 2013 revealed that it is possible to
artificially stimulate prior memories and artificially implant false
memories in mice. Using optogenetics,
a team of RIKEN-MIT scientists caused the mice to incorrectly associate
a benign environment with a prior unpleasant experience from different
surroundings. Some scientists believe that the study may have
implications in studying false memory formation in humans, and in
treating PTSD and schizophrenia.
Memory reconsolidation is when previously consolidated memories
are recalled or retrieved from long-term memory to your active
consciousness. During this process, memories can be further strengthened
and added to but there is also risk of manipulation involved. We like
to think of our memories as something stable and constant when they are
stored in long-term memory but this is not the case. There are a large
number of studies that found that consolidation of memories is not a
singular event but are put through the process again, known as
reconsolidation.
This is when a memory is recalled or retrieved and placed back into
your working memory. The memory is now open to manipulation from outside
sources and the misinformation effect which could be due to
misattributing the source of the inconsistent information, with or
without an intact original memory trace (Lindsay and Johnson, 1989). One thing that can be sure is that memory is malleable.
This new research into the concept of reconsolidation has opened
the door to methods to help those with unpleasant memories or those that
struggle with memories. An example of this is if you had a truly
frightening experience and recall that memory in a less arousing
environment, the memory will be weaken the next time it is retrieved.
"Some studies suggest that over-trained or strongly reinforced memories
do not undergo reconsolidation if reactivated the first few days after
training, but do become sensitive to reconsolidation interference with
time."
This, however does not mean that all memory is susceptible to
reconsolidation. There is evidence to suggest that memory that has
undergone strong training and whether or not is it intentional is less
likely to undergo reconsolidation.
There was further testing done with rats and mazes that showed that
reactivated memories were more susceptible to manipulation, in both good
and bad ways, than newly formed memories.
It is still not known whether or not these are new memories formed and
it is an inability to retrieve the proper one for the situation or if it
is a reconsolidated memory. Because the study of reconsolidation is
still a newer concept, there is still debate on whether it should be
considered scientifically sound.
A UCLA research study published in the June 2008 issue of the American Journal of Geriatric Psychiatry found that people can improve cognitive function and brain efficiency through simple lifestyle changes such as incorporating memory exercises, healthy eating, physical fitness and stress reduction
into their daily lives. This study examined 17 subjects, (average age
53) with normal memory performance.
Eight subjects were asked to follow a "brain healthy" diet, relaxation,
physical, and mental exercise (brain teasers and verbal memory training
techniques). After 14 days, they showed greater word fluency (not
memory) compared to their baseline performance. No long-term follow-up
was conducted; it is therefore unclear if this intervention has lasting
effects on memory.
There are a loosely associated group of mnemonic principles and
techniques that can be used to vastly improve memory known as the art of memory.
The International Longevity Center released in 2001 a report
which includes in pages 14–16 recommendations for keeping the mind in
good functionality until advanced age. Some of the recommendations are:
to stay intellectually active through learning, training or reading
to keep physically active so to promote blood circulation to the brain
to socialize
to reduce stress
to keep sleep time regular
to avoid depression or emotional instability
to observe good nutrition.
Memorization is a method of learning that allows an individual to recall information verbatim. Rote learning
is the method most often used. Methods of memorizing things have been
the subject of much discussion over the years with some writers, such as
Cosmos Rossellius using visual alphabets. The spacing effect
shows that an individual is more likely to remember a list of items
when rehearsal is spaced over an extended period of time. In contrast to
this is cramming: an intensive memorization in a short period of time. The spacing effect is exploited to improve memory in spaced repetition flashcard training. Also relevant is the Zeigarnik effect, which states that people remember uncompleted or interrupted tasks better than completed ones. The so-called Method of loci uses spatial memory to memorize non-spatial information.
In plants
Plants
lack a specialized organ devoted to memory retention, so plant memory
has been a controversial topic in recent years. New advances in the
field have identified the presence of neurotransmitters in plants, adding to the hypothesis that plants are capable of remembering. Action potentials, a physiological response characteristic of neurons, have been shown to have an influence on plants as well, including in wound responses and photosynthesis.
In addition to these homologous features of memory systems in both
plants and animals, plants have also been observed to encode, store and
retrieve basic short-term memories.
One of the most well-studied plants to show rudimentary memory is the Venus flytrap. Native to the subtropicalwetlands of the eastern United States, Venus flytraps have evolved the ability to obtain meat for sustenance, likely due to the lack of nitrogen in the soil.
This is done by two trap-forming leaf tips that snap shut once
triggered by a potential prey. On each lobe, three trigger hairs await
stimulation. In order to maximize the benefit-to-cost ratio, the plant
enables a rudimentary form of memory in which two trigger hairs must be
stimulated within thirty seconds in order to result in trap closure. This system ensures that the trap only closes when potential prey is within grasp.
The time lapse between trigger hair stimulations suggests that
the plant can remember an initial stimulus long enough for a second
stimulus to initiate trap closure. This memory is not encoded in a
brain, as plants lack this specialized organ. Rather, information is
stored in the form of cytoplasmic calcium levels. The first trigger causes a subthreshold cytoplasmic calcium influx.
This initial trigger is not enough to activate trap closure, so a
subsequent stimulus allows for a secondary influx of calcium. The latter
calcium rise superimposes on the initial one, creating an action
potential that passes threshold, resulting in trap closure.
Researchers, to prove that an electrical threshold must be met to
stimulate trap closure, excited a single trigger hair with a constant
mechanical stimulus using Ag/AgCl electrodes.
The trap closed after only a few seconds. This experiment demonstrated
that the electrical threshold, not necessarily the number of trigger
hair stimulations, was the contributing factor in Venus flytrap memory.
It has been shown that trap closure can be blocked using uncouplers and inhibitors of voltage-gated channels. After trap closure, these electrical signals stimulate glandular production of jasmonic acid and hydrolases, allowing for digestion of prey.
Many other plants exhibit the capacity to remember, including Mimosa pudica.
An experimental apparatus was designed to drop potted mimosa plants
repeatedly from the same distance and at the same speed. It was observed
that the plants' defensive response of curling up their leaves
decreased over the sixty times the experiment was repeated. To confirm
that this was a mechanism of memory rather than exhaustion,
some of the plants were shaken post experiment and displayed normal
defensive responses of leaf curling. This experiment demonstrated
long-term memory in the plants, as it was repeated a month later, and
the plants were observed to remain unfazed by the dropping.
A typical central nervous system synapse
The synapse and synaptic vesicle cycle
Major elements in chemical synaptic transmission
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