Intrinsically photosensitive retinal ganglion cells

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https://en.wikipedia.org/wiki/Intrinsically_photosensitive_retinal_ganglion_cells 

 

Section of retina: light strikes first the ganglion cell layer, last the rods and cones

 

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of ipRGCs were first noted in 1923 when rodless, coneless mice still responded to a light stimulus through pupil constriction, suggesting that rods and cones are not the only light-sensitive neurons in the retina. It wasn't until the 1980s that advancements in research on these cells began. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore they constitute a third class of photoreceptors, in addition to rod and cone cells.

Overview

Compared to the rods and cones, the ipRGCs respond more sluggishly and signal the presence of light over the long term. They represent a very small subset (~1%) of the retinal ganglion cells. Their functional roles are non-image-forming and fundamentally different from those of pattern vision; they provide a stable representation of ambient light intensity. They have at least three primary functions:

• They play a major role in synchronizing circadian rhythms to the 24-hour light/dark cycle, providing primarily length-of-day and length-of-night information. They send light information via the retinohypothalamic tract (RHT) directly to the circadian pacemaker of the brain, the suprachiasmatic nucleus of the hypothalamus. The physiological properties of these ganglion cells match known properties of the daily light entrainment (synchronization) mechanism regulating circadian rhythms. In addition, ipRGCs could also influence peripheral tissues such as the hair follicle regeneration through SCN-sympathetic nerve circuit.
• Photosensitive ganglion cells innervate other brain targets, such as the center of pupillary control, the olivary pretectal nucleus of the midbrain. They contribute to the regulation of pupil size and other behavioral responses to ambient lighting conditions.
• They contribute to photic regulation and acute photic suppression of release of the hormone melatonin.
• In rats, they play some role in conscious visual perception, including perception of regular gratings, light levels, and spatial information.

An ipRGC, shown here as a complied image of the retina from proximal inner nuclear layer to the ganglion cell layer with fluorescent labeling of melanopsin

 

Photoreceptive ganglion cells have been isolated in humans, where, in addition to regulating the circadian rhythm, they have been shown to mediate a degree of light recognition in rodless, coneless subjects suffering with disorders of rod and cone photoreceptors. Work by Farhan H. Zaidi and colleagues showed that photoreceptive ganglion cells may have some visual function in humans.

The photopigment of photoreceptive ganglion cells, melanopsin, is excited by light mainly in the blue portion of the visible spectrum (absorption peaks at ~480 nanometers). The phototransduction mechanism in these cells is not fully understood, but seems likely to resemble that in invertebrate rhabdomeric photoreceptors. In addition to responding directly to light, these cells may receive excitatory and inhibitory influences from rods and cones by way of synaptic connections in the retina.

The axons from these ganglia innervate regions of the brain related to object recognition, including the superior colliculus and dorsal lateral geniculate nucleus.

Structure

ipRGC receptor

Melanopsin structure

 

These photoreceptor cells project both throughout the retina and into the brain. They contain the photopigment melanopsin in varying quantities along the cell membrane, including on the axons up to the optic disc, the soma, and dendrites of the cell. ipRGCs contain membrane receptors for the neurotransmitters glutamate, glycine, and GABA. Photosensitive ganglion cells respond to light by depolarizing, thus increasing the rate at which they fire nerve impulses, which is opposite to that of other photoreceptor cells, which hyperpolarize in response to light.

Results of studies in mice suggest that the axons of ipRGCs are unmyelinated.

Melanopsin

Unlike other photoreceptor pigments, melanopsin has the ability to act as both the excitable photopigment and as a photoisomerase. Instead of requiring additional cells to revert between the two isoforms, from all-trans-retinal back into 11-cis-retinal before it can undergo another phototransduction, like the photoreceptor cones, which rely on Müller cells and retinal pigment epithelium cells for this conversion, melanopsin is able to isomerize all-trans-retinal into 11-cis-retinal when stimulated with light without help from additional cells. The two isoforms of melanopsin differ in their spectral sensitivity, for the 11-cis-retinal isoform is more responsive to shorter wavelengths of light, while the all-trans isoform is more responsive to longer wavelengths of light.

Synaptic inputs and outputs

Synaptic inputs and outputs of ipRGCs and their corresponding location in the brain

Inputs

ipRGCs are both pre- and postsynaptic to dopaminergic amacrine cells (DA cells) via reciprocal synapses, with ipRGCs sending excitatory signals to the DA cells, and the DA cells sending inhibitory signals to the ipRGCs. These inhibitory signals are mediated through GABA, which is co-released from the DA cells along with dopamine. Dopamine has functions in the light-adaptation process by up-regulating melanopsin transcription in ipRGCs and thus increasing the photoreceptor's sensitivity. In parallel with the DA amacrine cell inhibition, somatostatin-releasing amacrine cells, themselves inhibited by DA amacrine cells, inhibit ipRGCs. Other synaptic inputs to ipRGC dendrites include cone bipolar cells and rod bipolar cells.

Outputs

One postsynaptic target of ipRGCs is the suprachiasmatic nucleus (SCN) of the hypothalamus, which serves as the circadian clock in an organism. ipRGCs release both pituitary adenylyl cyclase-activating protein (PACAP) and glutamate onto the SCN via a monosynaptic connection called the retinohypothalamic tract (RHT). Glutamate has an excitatory effect on SCN neurons, and PACAP appears to enhance the effects of glutamate in the hypothalamus.

Other post synaptic targets of ipRGCs include: the intergenticulate leaflet (IGL), a cluster of neurons located in the thalamus, which play a role in circadian entrainment; the olivary pretectal nucleus (OPN), a cluster of neurons in the midbrain that controls the pupillary light reflex; the ventrolateral preoptic nucleus (VLPO), located in the hypothalamus and is a control center for sleep; as well as to the amygdala.

Function

Pupillary light reflex

Inputs and outputs to ipRGCs involved in the pupillary light reflex

 

Using various photoreceptor knockout mice, researchers have identified the role of ipRGCs in both the transient and sustained signaling of the pupillary light reflex (PLR). Transient PLR occurs at dim to moderate light intensities and is a result of phototransduction occurring in rod cells, which provide synaptic input onto ipRGCs, which in turn relay the information to the olivary pretectal nucleus in the midbrain. The neurotransmitter involved in the relay of information to the midbrain from the ipRGCs in the transient PLR is glutamate. At brighter light intensities the sustained PLR occurs, which involves both phototransduction of the rod providing input to the ipRGCs and phototransduction of the ipRGCs themselves via melanopsin. Researchers have suggested that the role of melanopsin in the sustained PLR is due to its lack of adaptation to light stimuli in contrast to rod cells, which exhibit adaptation. The sustained PLR is maintained by PACAP release from ipRGCs in a pulsatile manner.

Possible role in conscious sight

Experiments with rodless, coneless humans allowed another possible role for the receptor to be studied. In 2007, a new role was found for the photoreceptive ganglion cell. Zaidi and colleagues showed that in humans the retinal ganglion cell photoreceptor contributes to conscious sight as well as to non-image-forming functions like circadian rhythms, behaviour and pupillary reactions.^[6] Since these cells respond mostly to blue light, it has been suggested that they have a role in mesopic vision^{[citation needed]} and that the old theory of a purely duplex retina with rod (dark) and cone (light) light vision was simplistic. Zaidi and colleagues' work with rodless, coneless human subjects hence has also opened the door into image-forming (visual) roles for the ganglion cell photoreceptor.

The discovery that there are parallel pathways for vision was made: one classic rod- and cone-based arising from the outer retina, the other a rudimentary visual brightness detector arising from the inner retina. The latter seems to be activated by light before the former.^[6] Classic photoreceptors also feed into the novel photoreceptor system, and colour constancy may be an important role as suggested by Foster^{[citation needed]}.

It has been suggested by the authors of the rodless, coneless human model that the receptor could be instrumental in understanding many diseases, including major causes of blindness worldwide such as glaucoma, a disease which affects ganglion cells.

In other mammals, photosensitive ganglia have proven to have a genuine role in conscious vision. Tests conducted by Jennifer Ecker et al. found that rats lacking rods and cones were able to learn to swim toward sequences of vertical bars rather than an equally luminescent gray screen.^[5]

Violet-to-blue light

Most work suggests that the peak spectral sensitivity of the receptor is between 460 and 484 nm. Lockley et al. in 2003^[16] showed that 460 nm (blue) wavelengths of light suppress melatonin twice as much as 555 nm (green) light, the peak sensitivity of the photopic visual system. In work by Zaidi, Lockley and co-authors using a rodless, coneless human, it was found that a very intense 481 nm stimulus led to some conscious light perception, meaning that some rudimentary vision was realized.^[6]

Discovery

In 1923, Clyde E. Keeler observed that the pupils in the eyes of blind mice he had accidentally bred still responded to light.^[17] The ability of the rodless, coneless mice to retain a pupillary light reflex was suggestive of an additional photoreceptor cell.^[8]

In the 1980s, research in rod- and cone-deficient rats showed regulation of dopamine in the retina, a known neuromodulator for light adaptation and photoentrainment.^[1]

Research continued in 1991, when Russell G. Foster and colleagues, including Ignacio Provencio, showed that rods and cones were not necessary for photoentrainment, the visual drive of the circadian rhythm, nor for the regulation of melatonin secretion from the pineal gland, via rod- and cone-knockout mice.^[18][8] Later work by Provencio and colleagues showed that this photoresponse was mediated by the photopigment melanopsin, present in the ganglion cell layer of the retina.^[19]

The photoreceptors were identified in 2002 by Samer Hattar, David Berson and colleagues, where they were shown to be melanopsin expressing ganglion cells that possessed an intrinsic light response and projected to a number of brain areas involved in non-image-forming vision.^[20][21]

In 2005, Panda, Melyan, Qiu, and colleagues demonstrated that the melanopsin photopigment was the phototransduction pigment in ganglion cells.^[22][23] Dennis Dacey and colleagues showed in a species of Old World monkey that giant ganglion cells expressing melanopsin projected to the lateral geniculate nucleus (LGN).^[24][3] Previously only projections to the midbrain (pre-tectal nucleus) and hypothalamus (supra-chiasmatic nuclei, SCN) had been shown. However, a visual role for the receptor was still unsuspected and unproven.

Research

Research in humans

Attempts were made to hunt down the receptor in humans, but humans posed special challenges and demanded a new model. Unlike in other animals, researchers could not ethically induce rod and cone loss either genetically or with chemicals so as to directly study the ganglion cells. For many years, only inferences could be drawn about the receptor in humans, though these were at times pertinent.

In 2007, Zaidi and colleagues published their work on rodless, coneless humans, showing that these people retain normal responses to nonvisual effects of light. The identity of the non-rod, non-cone photoreceptor in humans was found to be a ganglion cell in the inner retina as shown previously in rodless, coneless models in some other mammals. The work was done using patients with rare diseases that wiped out classic rod and cone photoreceptor function but preserved ganglion cell function. Despite having no rods or cones, the patients continued to exhibit circadian photoentrainment, circadian behavioural patterns, melatonin suppression, and pupil reactions, with peak spectral sensitivities to environmental and experimental light that match the melanopsin photopigment. Their brains could also associate vision with light of this frequency. Clinicians and scientists are now seeking to understand the new receptor's role in human diseases and blindness.

Photoreceptor cell

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Photoreceptor_cell 

Photoreceptor cell
Functional parts of the rods and cones, which are two of the three types of photosensitive cells in the retina
Identifiers
MeSH	D010786

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiation) into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

There are currently three known types of photoreceptor cells in mammalian eyes: rods, cones, and intrinsically photosensitive retinal ganglion cells. The two classic photoreceptor cells are rods and cones, each contributing information used by the visual system to form a representation of the visual world, sight. The rods are narrower than the cones and distributed differently across the retina, but the chemical process in each that supports phototransduction is similar. A third class of mammalian photoreceptor cell was discovered during the 1990s: the intrinsically photosensitive retinal ganglion cells. These cells do not contribute to sight directly, but are thought to support circadian rhythms and pupillary reflex.

There are major functional differences between the rods and cones. Rods are extremely sensitive, and can be triggered by a single photon. At very low light levels, visual experience is based solely on the rod signal. 

Cones require significantly brighter light (that is, a larger number of photons) to produce a signal. In humans, there are three different types of cone cell, distinguished by their pattern of response to light of different wavelengths. Color experience is calculated from these three distinct signals, perhaps via an opponent process. This explains why colors cannot be seen at low light levels, when only the rod and not the cone photoreceptor cells are active. The three types of cone cell respond (roughly) to light of short, medium, and long wavelengths, so they may respectively be referred to as S-cones, M-cones, and L-cones. 

In accordance with the principle of univariance, the firing of the cell depends upon only the number of photons absorbed. The different responses of the three types of cone cells are determined by the likelihoods that their respective photoreceptor proteins will absorb photons of different wavelengths. So, for example, an L cone cell contains a photoreceptor protein that more readily absorbs long wavelengths of light (that is, more "red"). Light of a shorter wavelength can also produce the same response from an L cone cell, but it must be much brighter to do so.

The human retina contains about 120 million rod cells, and 6 million cone cells. The number and ratio of rods to cones varies among species, dependent on whether an animal is primarily diurnal or nocturnal. Certain owls, such as the nocturnal tawny owl, have a tremendous number of rods in their retinae. In the human visual system, in addition to the photosensitive rods & cones, there are about 2.4 million to 3 million ganglion cells, with 1 to 2% of them being photosensitive. The axons of ganglion cells form the two optic nerves.

Photoreceptor cells are typically arranged in an irregular but approximately hexagonal grid, known as the retinal mosaic.

The pineal and parapineal glands are photoreceptive in non-mammalian vertebrates, but not in mammals. Birds have photoactive cerebrospinal fluid (CSF)-contacting neurons within the paraventricular organ that respond to light in the absence of input from the eyes or neurotransmitters. Invertebrate photoreceptors in organisms such as insects and molluscs are different in both their morphological organization and their underlying biochemical pathways. This article describes human photoreceptors.

Histology

Anatomy of rods and cones varies slightly.

Rod and cone photoreceptors are found on the outermost layer of the retina; they both have the same basic structure. Closest to the visual field (and farthest from the brain) is the axon terminal, which releases a neurotransmitter called glutamate to bipolar cells. Farther back is the cell body, which contains the cell's organelles. Farther back still is the inner segment, a specialized part of the cell full of mitochondria. The chief function of the inner segment is to provide ATP (energy) for the sodium-potassium pump. Finally, closest to the brain (and farthest from the field of view) is the outer segment, the part of the photoreceptor that absorbs light. Outer segments are actually modified cilia that contain disks filled with opsin, the molecule that absorbs photons, as well as voltage-gated sodium channels.

The membranous photoreceptor protein opsin contains a pigment molecule called retinal. In rod cells, these together are called rhodopsin. In cone cells, there are different types of opsins that combine with retinal to form pigments called photopsins. Three different classes of photopsins in the cones react to different ranges of light frequency, a differentiation that allows the visual system to calculate color. The function of the photoreceptor cell is to convert the light energy of the photon into a form of energy communicable to the nervous system and readily usable to the organism: This conversion is called signal transduction.

The opsin found in the intrinsically photosensitive ganglion cells of the retina is called melanopsin. These cells are involved in various reflexive responses of the brain and body to the presence of (day)light, such as the regulation of circadian rhythms, pupillary reflex and other non-visual responses to light. Melanopsin functionally resembles invertebrate opsins.

When light activates the melanopsin signaling system, the melanopsin-containing ganglion cells discharge nerve impulses that are conducted through their axons to specific brain targets. These targets include the olivary pretectal nucleus (a center responsible for controlling the pupil of the eye), the LGN, and, through the retinohypothalamic tract (RHT), the suprachiasmatic nucleus of the hypothalamus (the master pacemaker of circadian rhythms). Melanopsin-containing ganglion cells are thought to influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP).

Humans

Normalized human photoreceptor absorbances for different wavelengths of light

 

Illustration of the distribution of cone cells in the fovea of an individual with normal color vision (left), and a color blind (protanopic) retina. Note that the center of the fovea holds very few blue-sensitive cones.

 

Distribution of rods and cones along a line passing through the fovea and the blind spot of a human eye

 

The human retina has approximately 6 million cones and 120 million rods. Signals from the rods and cones converge on ganglion and bipolar cells for preprocessing before they are sent to the lateral geniculate nucleus. At the "center" of the retina (the point directly behind the lens) lies the fovea (or fovea centralis), which contains only cone cells; and is the region capable of producing the highest visual acuity or highest resolution. Across the rest of the retina, rods and cones are intermingled. No photoreceptors are found at the blind spot, the area where ganglion cell fibers are collected into the optic nerve and leave the eye.

The photoreceptor proteins in the three types of cones differ in their sensitivity to photons of different wavelengths (see graph). Since cones respond to both the wavelength and intensity of light, the cone's sensitivity to wavelength is measured in terms of its relative rate of response if the intensity of a stimulus is held fixed, while the wavelength is varied. From this, in turn, is inferred the absorbance. The graph normalizes the degree of absorbance on a hundred-point scale. For example, the S cone's relative response peaks around 420 nm (nanometers, a measure of wavelength). This tells us that an S cone is more likely to absorb a photon at 420 nm than at any other wavelength. If light of a different wavelength to which it is less sensitive, say 480 nm, is increased in brightness appropriately, however, it will produce exactly the same response in the S cone. So, the colors of the curves are misleading. Cones cannot detect color by themselves; rather, color vision requires comparison of the signal across different cone types.

Phototransduction

The process of phototransduction occurs in the retina. The retina has many layers of various cell types. The most numerous photoreceptor cells (rods and cones) form the outermost layer. These are the photoreceptors responsible for mediating the sense sight. The middle retinal layer contains bipolar cells, collect signals from photoreceptors and transmit them to the retinal ganglion cells of the innermost retinal layer. Retinal ganglion cell axons collectively form the optic nerve, via which they project to the brain.

 

Unlike most sensory receptor cells, photoreceptors actually become hyperpolarized when stimulated; and conversely are depolarized when not stimulated. This means that glutamate is released continuously when the cell is unstimulated, and stimulus causes release to stop. In the dark, cells have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which opens cGMP-gated ion channels. These channels are nonspecific, allowing movement of both sodium and calcium ions when open. The movement of these positively charged ions into the cell (driven by their respective electrochemical gradient) depolarizes the membrane, and leads to the release of the neurotransmitter glutamate. 

When light hits a photoreceptive pigment within the photoreceptor cell, the pigment changes shape. The pigment, called iodopsin or rhodopsin, consists of large proteins called opsin (situated in the plasma membrane), attached to a covalently bound prosthetic group: an organic molecule called retinal (a derivative of vitamin A). The retinal exists in the 11-cis-retinal form when in the dark, and stimulation by light causes its structure to change to all-trans-retinal. This structural change causes opsin (a G protein-coupled receptor) to activate its G protein transducin, which leads to the activation of cGMP phosphodiesterase, which breaks cGMP down into 5'-GMP. Reduction in cGMP allows the ion channels to close, preventing the influx of positive ions, hyperpolarizing the cell, and stopping the release of neurotransmitters. The entire process by which light initiates a sensory response is called visual phototransduction.

Dark current

Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound to them. Hence, positively charged ions (namely sodium ions) enter the photoreceptor, depolarizing it to about −40 mV (resting potential in other nerve cells is usually −65 mV). This depolarization current is often known as dark current.

Signal transduction pathway

The absorption of light leads to an isomeric change in the retinal molecule.

 

The signal transduction pathway is the mechanism by which the energy of a photon signals a mechanism in the cell that leads to its electrical polarization. This polarization ultimately leads to either the transmittance or inhibition of a neural signal that will be fed to the brain via the optic nerve. The steps, or signal transduction pathway, in the vertebrate eye's rod and cone photoreceptors are then:

1. The rhodopsin or iodopsin in the disc membrane of the outer segment absorbs a photon, changing the configuration of a retinal Schiff base cofactor inside the protein from the cis-form to the trans-form, causing the retinal to change shape.
2. This results in a series of unstable intermediates, the last of which binds stronger to a G protein in the membrane, called transducin, and activates it. This is the first amplification step – each photoactivated rhodopsin triggers activation of about 100 transducins.
3. Each transducin then activates the enzyme cGMP-specific phosphodiesterase (PDE).
4. PDE then catalyzes the hydrolysis of cGMP to 5' GMP. This is the second amplification step, where a single PDE hydrolyses about 1000 cGMP molecules.
5. The net concentration of intracellular cGMP is reduced (due to its conversion to 5' GMP via PDE), resulting in the closure of cyclic nucleotide-gated Na⁺ ion channels located in the photoreceptor outer segment membrane.
6. As a result, sodium ions can no longer enter the cell, and the photoreceptor outer segment membrane becomes hyperpolarized, due to the charge inside the membrane becoming more negative.
7. This change in the cell's membrane potential causes voltage-gated calcium channels to close. This leads to a decrease in the influx of calcium ions into the cell and thus the intracellular calcium ion concentration falls.
8. A decrease in the intracellular calcium concentration means that less glutamate is released via calcium-induced exocytosis to the bipolar cell (see below). (The decreased calcium level slows the release of the neurotransmitter glutamate, which excites the postsynaptic bipolar cells and horizontal cells.)
9. Reduction in the release of glutamate means one population of bipolar cells will be depolarized and a separate population of bipolar cells will be hyperpolarized, depending on the nature of receptors (ionotropic or metabotropic) in the postsynaptic terminal.

Thus, a rod or cone photoreceptor actually releases less neurotransmitter when stimulated by light. Less neurotransmitter in the synaptic cleft between a photoreceptor and bipolar cell will serve to either excite (depolarize) ON bipolar cells or inhibit (hyperpolarize) OFF bipolar cells. Thus, it is at the photoreceptor-bipolar cell synapse where visual signals are split into ON and OFF pathways.

ATP provided by the inner segment powers the sodium-potassium pump. This pump is necessary to reset the initial state of the outer segment by taking the sodium ions that are entering the cell and pumping them back out. 

Although photoreceptors are neurons, they do not conduct action potentials with the exception of the photosensitive ganglion cell – which are involved mainly in the regulation of circadian rhythms, melatonin, and pupil dilation.

Advantages

Phototransduction in rods and cones is somewhat unusual in that the stimulus (in this case, light) reduces the cell's response or firing rate, different from most other sensory systems in which a stimulus increases the cell's response or firing rate. This difference has important functional consequences:

First, the classic (rod or cone) photoreceptor is depolarized in the dark, which means many sodium ions are flowing into the cell. Thus, the random opening or closing of sodium channels will not affect the membrane potential of the cell; only the closing of a large number of channels, through absorption of a photon, will affect it and signal that light is in the visual field. This system may have less noise relative to sensory transduction schema that increase rate of neural firing in response to stimulus, like touch and olfaction.

Second, there is a lot of amplification in two stages of classic phototransduction: one pigment will activate many molecules of transducin, and one PDE will cleave many cGMPs. This amplification means that even the absorption of one photon will affect membrane potential and signal to the brain that light is in the visual field. This is the main feature that differentiates rod photoreceptors from cone photoreceptors. Rods are extremely sensitive and have the capacity of registering a single photon of light, unlike cones. On the other hand, cones are known to have very fast kinetics in terms of rate of amplification of phototransduction, unlike rods.

Difference between rods and cones

Comparison of human rod and cone cells, from Eric Kandel et al. in Principles of Neural Science.

Rods	Cones
Used for scotopic vision (vision under low light conditions)	Used for photopic vision (vision under high light conditions)
Very light sensitive; sensitive to scattered light	Not very light sensitive; sensitive only to direct light
Loss causes night blindness	Loss causes legal blindness
Low visual acuity	High visual acuity; better spatial resolution
Not present in fovea	Concentrated in fovea
Slow response to light, stimuli added over time	Fast response to light, can perceive more rapid changes in stimuli
Have more pigment than cones, so can detect lower light levels	Have less pigment than rods, require more light to detect images
Stacks of membrane-enclosed disks are unattached to cell membrane directly	Disks are attached to outer membrane
About 120 million rods distributed around the retina	About 6 million cones distributed in each retina
One type of photosensitive pigment	Three types of photosensitive pigment in humans
Confer achromatic vision	Confer color vision

Function

Photoreceptors signals color; they only signal the presence of light in the visual field.

A given photoreceptor responds to both the wavelength and intensity of a light source. For example, red light at a certain intensity can produce the same exact response in a photoreceptor as the green light of different intensity. Therefore, the response of a single photoreceptor is ambiguous when it comes to color.

Development

The key events mediating rod versus S cone versus M cone differentiation are induced by several transcription factors, including RORbeta, OTX2, NRL, CRX, NR2E3 and TRbeta2. The S cone fate represents the default photoreceptor program, however differential transcriptional activity can bring about rod or M cone generation. L cones are present in primates, however there is not much known for their developmental program due to use of rodents in research. There are five steps to developing photoreceptors: proliferation of multi-potent retinal progenitor cells (RPCs); restriction of competence of RPCs; cell fate specification; photoreceptor gene expression; and lastly axonal growth, synapse formation and outer segment growth.

Early Notch signaling maintains progenitor cycling. Photoreceptor precursors come about through inhibition of Notch signaling and increased activity of various factors including achaete-scute homologue 1. OTX2 activity commits cells to the photoreceptor fate. CRX further defines the photoreceptor specific panel of genes being expressed. NRL expression leads to the rod fate. NR2E3 further restricts cells to the rod fate by repressing cone genes. RORbeta is needed for both rod and cone development. TRbeta2 mediates the M cone fate. If any of the previously mentioned factors' functions are ablated, the default photoreceptor is a S cone. These events take place at different time periods for different species and include a complex pattern of activities that bring about a spectrum of phenotypes. If these regulatory networks are disrupted, retinitis pigmentosa, macular degeneration or other visual deficits may result.

Signaling

3D medical illustration of the rod and cone structure of photoreceptors.

The rod and cone photoreceptors signal their absorption of photons via a decrease in the release of the neurotransmitter glutamate to bipolar cells at its axon terminal. Since the photoreceptor is depolarized in the dark, a high amount of glutamate is being released to bipolar cells in the dark. Absorption of a photon will hyperpolarize the photoreceptor and therefore result in the release of less glutamate at the presynaptic terminal to the bipolar cell.

Every rod or cone photoreceptor releases the same neurotransmitter, glutamate. However, the effect of glutamate differs in the bipolar cells, depending upon the type of receptor imbedded in that cell's membrane. When glutamate binds to an ionotropic receptor, the bipolar cell will depolarize (and therefore will hyperpolarize with light as less glutamate is released). On the other hand, binding of glutamate to a metabotropic receptor results in a hyperpolarization, so this bipolar cell will depolarize to light as less glutamate is released.

In essence, this property allows for one population of bipolar cells that gets excited by light and another population that gets inhibited by it, even though all photoreceptors show the same response to light. This complexity becomes both important and necessary for detecting color, contrast, edges, etc.

Further complexity arises from the various interconnections among bipolar cells, horizontal cells, and amacrine cells in the retina. The final result is differing populations of ganglion cells in the retina, a sub-population of which is also intrinsically photosensitive, using the photopigment melanopsin.

Ganglion cell (non-rod non-cone) photoreceptors

A non-rod non-cone photoreceptor in the eyes of mice, which was shown to mediate circadian rhythms, was discovered in 1991 by Foster et al. These neuronal cells, called intrinsically photosensitive retinal ganglion cells (ipRGC), are a small subset (≈1–3%) of the retinal ganglion cells located in the inner retina, that is, in front of the rods and cones located in the outer retina. These light sensitive neurons contain a photopigment, melanopsin, which has an absorption peak of the light at a different wavelength (≈480 nm) than rods and cones. Beside circadian / behavioral functions, ipRGCs have a role in initiating the pupillary light reflex.

Dennis Dacey with colleagues showed in a species of Old World monkey that giant ganglion cells expressing melanopsin projected to the lateral geniculate nucleus (LGN). Previously only projections to the midbrain (pre-tectal nucleus) and hypothalamus (suprachiasmatic nucleus) had been shown. However a visual role for the receptor was still unsuspected and unproven.

In 2007, Farhan H. Zaidi and colleagues published pioneering work using rodless coneless humans. Current Biology subsequently announced in their 2008 editorial, commentary and despatches to scientists and ophthalmologists, that the non-rod non-cone photoreceptor had been conclusively discovered in humans using landmark experiments on rodless coneless humans by Zaidi and colleagues As had been found in other mammals, the identity of the non-rod non-cone photoreceptor in humans was found to be a ganglion cell in the inner retina. The workers had tracked down patients with rare diseases wiping out classic rod and cone photoreceptor function but preserving ganglion cell function. Despite having no rods or cones the patients continued to exhibit circadian photoentrainment, circadian behavioural patterns, melanopsin suppression, and pupil reactions, with peak spectral sensitivities to environmental and experimental light matching that for the melanopsin photopigment. Their brains could also associate vision with light of this frequency. 

In humans the retinal ganglion cell photoreceptor contributes to conscious sight as well as to non-image-forming functions like circadian rhythms, behaviour and pupil reactions. Since these cells respond mostly to blue light, it has been suggested that they have a role in mesopic vision. Zaidi and colleagues' work with rodless coneless human subjects hence also opened the door into image-forming (visual) roles for the ganglion cell photoreceptor. It was discovered that there are parallel pathways for vision – one classic rod and cone-based pathway arising from the outer retina, and the other a rudimentary visual brightness detector pathway arising from the inner retina, which seems to be activated by light before the other. Classic photoreceptors also feed into the novel photoreceptor system, and color constancy may be an important role as suggested by Foster. The receptor could be instrumental in understanding many diseases including major causes of blindness worldwide like glaucoma, a disease that affects ganglion cells, and the study of the receptor offered potential as a new avenue to explore in trying to find treatments for blindness. It is in these discoveries of the novel photoreceptor in humans and in the receptor's role in vision, rather than its non-image-forming functions, where the receptor may have the greatest impact on society as a whole, though the impact of disturbed circadian rhythms is another area of relevance to clinical medicine. 

Most work suggests that the peak spectral sensitivity of the receptor is between 460 and 482 nm. Steven Lockley et al. in 2003 showed that 460 nm wavelengths of light suppress melatonin twice as much as longer 555 nm light. However, in more recent work by Farhan Zaidi et al., using rodless coneless humans, it was found that what consciously led to light perception was a very intense 481 nm stimulus; this means that the receptor, in visual terms, enables some rudimentary vision maximally for blue light.

Sensory nervous system

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Sensory_nervous_system 

 

Sensory nervous system
Typical sensory system: the visual system, illustrated by the classic Gray's FIG. 722– This scheme shows the flow of information from the eyes to the central connections of the optic nerves and optic tracts, to the visual cortex. Area V1 is the region of the brain which is engaged in vision.
Details
Identifiers
Latin	organa sensuum
MeSH	D012679
TA	A15.0.00.000
FMA	75259

The visual system and the somatosensory system are active even during resting state fMRI

 

 

Activation and response in the sensory nervous system

 

The sensory nervous system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory neurons (including the sensory receptor cells), neural pathways, and parts of the brain involved in sensory perception. Commonly recognized sensory systems are those for vision, hearing, touch, taste, smell, and balance. In short, senses are transducers from the physical world to the realm of the mind where we interpret the information, creating our perception of the world around us.

Organisms need information to solve at least three kinds of problems: (a) to maintain an appropriate environment, i.e., homeostasis; (b) to time activities (e.g., seasonal changes in behavior) or synchronize activities with those of conspecifics; and (c) to locate and respond to resources or threats (e.g., by moving towards resources or evading or attacking threats). Organisms also need to transmit information in order to influence another's behavior: to identify themselves, warn conspecifics of danger, coordinate activities, or deceive.

The receptive field is the area of the body or environment to which a receptor organ and receptor cells respond. For instance, the part of the world an eye can see, is its receptive field; the light that each rod or cone can see, is its receptive field. Receptive fields have been identified for the visual system, auditory system and somatosensory system.

Stimulus

Sensory systems code for four aspects of a stimulus; type (modality), intensity, location, and duration. Arrival time of a sound pulse and phase differences of continuous sound are used for sound localization. Certain receptors are sensitive to certain types of stimuli (for example, different mechanoreceptors respond best to different kinds of touch stimuli, like sharp or blunt objects). Receptors send impulses in certain patterns to send information about the intensity of a stimulus (for example, how loud a sound is). The location of the receptor that is stimulated gives the brain information about the location of the stimulus (for example, stimulating a mechanoreceptor in a finger will send information to the brain about that finger). The duration of the stimulus (how long it lasts) is conveyed by firing patterns of receptors. These impulses are transmitted to the brain through afferent neurons.

Senses and receptors

While debate exists among neurologists as to the specific number of senses due to differing definitions of what constitutes a sense, Gautama Buddha and Aristotle classified five ‘traditional’ human senses which have become universally accepted: touch, taste, smell, sight, and hearing. Other senses that have been well-accepted in most mammals, including humans, include nociception, equilibrioception, kinaesthesia, and thermoception. Furthermore, some nonhuman animals have been shown to possess alternate senses, including magnetoception and electroreception.

Receptors

The initialization of sensation stems from the response of a specific receptor to a physical stimulus. The receptors which react to the stimulus and initiate the process of sensation are commonly characterized in four distinct categories: chemoreceptors, photoreceptors, mechanoreceptors, and thermoreceptors. All receptors receive distinct physical stimuli and transduce the signal into an electrical action potential. This action potential then travels along afferent neurons to specific brain regions where it is processed and interpreted.

Chemoreceptors

Chemoreceptors, or chemosensors, detect certain chemical stimuli and transduce that signal into an electrical action potential. The two primary types of chemoreceptors are:

• Distance chemoreceptors are integral to receiving stimuli in gases in the olfactory system through both olfactory receptor neurons and neurons in the vomeronasal organ.
• Direct chemoreceptors that detect stimuli in liquids include the taste buds in the gustatory system as well as receptors in the aortic bodies which detect changes in oxygen concentration.

Photoreceptors

Photoreceptors are capable of phototransduction, a process which converts light (electromagnetic radiation) into, among other types of energy, a membrane potential. The three primary types of photoreceptors are: Cones are photoreceptors which respond significantly to color. In humans the three different types of cones correspond with a primary response to short wavelength (blue), medium wavelength (green), and long wavelength (yellow/red). Rods are photoreceptors which are very sensitive to the intensity of light, allowing for vision in dim lighting. The concentrations and ratio of rods to cones is strongly correlated with whether an animal is diurnal or nocturnal. In humans rods outnumber cones by approximately 20:1, while in nocturnal animals, such as the tawny owl, the ratio is closer to 1000:1. Ganglion Cells reside in the adrenal medulla and retina where they are involved in the sympathetic response. Of the ~1.3 million ganglion cells present in the retina, 1-2% are believed to be photosensitive ganglia. These photosensitive ganglia play a role in conscious vision for some animals, and are believed to do the same in humans.

Mechanoreceptors

Mechanoreceptors are sensory receptors which respond to mechanical forces, such as pressure or distortion. While mechanoreceptors are present in hair cells and play an integral role in the vestibular and auditory systems, the majority of mechanoreceptors are cutaneous and are grouped into four categories:

• Slowly adapting type 1 receptors have small receptive fields and respond to static stimulation. These receptors are primarily used in the sensations of form and roughness.
• Slowly adapting type 2 receptors have large receptive fields and respond to stretch. Similarly to type 1, they produce sustained responses to a continued stimuli.
• Rapidly adapting receptors have small receptive fields and underlie the perception of slip.
• Pacinian receptors have large receptive fields and are the predominant receptors for high-frequency vibration.

Thermoreceptors

Thermoreceptors are sensory receptors which respond to varying temperatures. While the mechanisms through which these receptors operate is unclear, recent discoveries have shown that mammals have at least two distinct types of thermoreceptors:

• The end-bulb of Krause, or bulboid corpuscle, detects temperatures above body temperature.
• Ruffini’s end organ detects temperatures below body temperature.

TRPV1 is a heat-activated channel that acts as a small heat detecting thermometer in the membrane which begins the polarization of the neural fiber when exposed to changes in temperature. Ultimately, this allows us to detect ambient temperature in the warm/hot range. Similarly, the molecular cousin to TRPV1, TRPM8, is a cold-activated ion channel that responds to cold. Both cold and hot receptors are segregated by distinct subpopulations of sensory nerve fibers, which shows us that the information coming into the spinal cord is originally separate. Each sensory receptor has its own “labeled line” to convey a simple sensation experienced by the recipient. Ultimately, TRP channels act as thermosensors, channels that help us to detect changes in ambient temperatures.

Nociceptors

Nociceptors respond to potentially damaging stimuli by sending signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain. They are found in internal organs, as well as on the surface of the body. Nociceptors detect different kinds of damaging stimuli or actual damage. Those that only respond when tissues are damaged are known as "sleeping" or "silent" nociceptors.

• Thermal nociceptors are activated by noxious heat or cold at various temperatures.
• Mechanical nociceptors respond to excess pressure or mechanical deformation.
• Chemical nociceptors respond to a wide variety of chemicals, some of which are signs of tissue damage. They are involved in the detection of some spices in food.

Sensory cortex

All stimuli received by the receptors listed above are transduced to an action potential, which is carried along one or more afferent neurons towards a specific area of the brain. While the term sensory cortex is often used informally to refer to the somatosensory cortex, the term more accurately refers to the multiple areas of the brain at which senses are received to be processed. For the five traditional senses in humans, this includes the primary and secondary cortices of the different senses: the somatosensory cortex, the visual cortex, the auditory cortex, the primary olfactory cortex, and the gustatory cortex. Other modalities have corresponding sensory cortex areas as well, including the vestibular cortex for the sense of balance.

Somatosensory cortex

Located in the parietal lobe, the primary somatosensory cortex is the primary receptive area for the sense of touch and proprioception in the somatosensory system. This cortex is further divided into Brodmann areas 1, 2, and 3. Brodmann area 3 is considered the primary processing center of the somatosensory cortex as it receives significantly more input from the thalamus, has neurons highly responsive to somatosensory stimuli, and can evoke somatic sensations through electrical stimulation. Areas 1 and 2 receive most of their input from area 3. There are also pathways for proprioception (via the cerebellum), and motor control (via Brodmann area 4). See also: S2 Secondary somatosensory cortex.

The human eye is the first element of a sensory system: in this case, vision, for the visual system.

Visual cortex

The visual cortex refers to the primary visual cortex, labeled V1 or Brodmann area 17, as well as the extrastriate visual cortical areas V2-V5. Located in the occipital lobe, V1 acts as the primary relay station for visual input, transmitting information to two primary pathways labeled the dorsal and ventral streams. The dorsal stream includes areas V2 and V5, and is used in interpreting visual ‘where’ and ‘how.’ The ventral stream includes areas V2 and V4, and is used in interpreting ‘what.’ Increases in Task-negative activity are observed in the ventral attention network, after abrupt changes in sensory stimuli, at the onset and offset of task blocks, and at the end of a completed trial.

Ear

Auditory cortex

Located in the temporal lobe, the auditory cortex is the primary receptive area for sound information. The auditory cortex is composed of Brodmann areas 41 and 42, also known as the anterior transverse temporal area 41 and the posterior transverse temporal area 42, respectively. Both areas act similarly and are integral in receiving and processing the signals transmitted from auditory receptors. 

Nose

Primary olfactory cortex

Located in the temporal lobe, the primary olfactory cortex is the primary receptive area for olfaction, or smell. Unique to the olfactory and gustatory systems, at least in mammals, is the implementation of both peripheral and central mechanisms of action. The peripheral mechanisms involve olfactory receptor neurons which transduce a chemical signal along the olfactory nerve, which terminates in the olfactory bulb. The chemoreceptors in the receptor neurons that start the signal cascade are G protein-coupled receptors. The central mechanisms include the convergence of olfactory nerve axons into glomeruli in the olfactory bulb, where the signal is then transmitted to the anterior olfactory nucleus, the piriform cortex, the medial amygdala, and the entorhinal cortex, all of which make up the primary olfactory cortex. 

In contrast to vision and hearing, the olfactory bulbs are not cross-hemispheric; the right bulb connects to the right hemisphere and the left bulb connects to the left hemisphere. 

Tongue

Gustatory cortex

The gustatory cortex is the primary receptive area for taste. The word taste is used in a technical sense to refer specifically to sensations coming from taste buds on the tongue. The five qualities of taste detected by the tongue include sourness, bitterness, sweetness, saltiness, and the protein taste quality, called umami. In contrast, the term flavor refers to the experience generated through integration of taste with smell and tactile information. The gustatory cortex consists of two primary structures: the anterior insula, located on the insular lobe, and the frontal operculum, located on the frontal lobe. Similarly to the olfactory cortex, the gustatory pathway operates through both peripheral and central mechanisms. Peripheral taste receptors, located on the tongue, soft palate, pharynx, and esophagus, transmit the received signal to primary sensory axons, where the signal is projected to the nucleus of the solitary tract in the medulla, or the gustatory nucleus of the solitary tract complex. The signal is then transmitted to the thalamus, which in turn projects the signal to several regions of the neocortex, including the gustatory cortex.

The neural processing of taste is affected at nearly every stage of processing by concurrent somatosensory information from the tongue, that is, mouthfeel. Scent, in contrast, is not combined with taste to create flavor until higher cortical processing regions, such as the insula and orbitofrontal cortex.

Human sensory system

The human sensory system consists of the following subsystems:

• Visual system
• Auditory system
• Somatosensory system consists of the receptors, transmitters (pathways) leading to S1, and S1 that experiences the sensations labelled as touch, pressure, vibration, temperature (warm or cold), pain (including itch and tickle), and the sensations of muscle movement and joint position including posture, movement, and facial expression (collectively also called proprioception)
• Gustatory system
• Olfactory system
• Vestibular system

Diseases

Disability-adjusted life year for sense organ diseases per 100,000 inhabitants in 2002.

  no data

  less than 200

  200-400

  400-600

  600-800

  800-1000

  1000-1200

  1200-1400

  1400-1600

  1600-1800

  1800-2000

  2000-2300

  more than 2300

• Amblyopia
• Anacusis
• Color blindness
• Deafness