Retinal Ganglion Cell
Retinal ganglion cells are neurons in the vertebrate retina.
Retinal ganglion cells (RGCs) are found in the innermost layer of the retina. They integrate information from photoreceptors, via the bipolar cells of the retina, and project into the brain, where they synapse at the thalamus, the hypothalamus and the superior colliculus (1). Some RGCs are themselves photoreceptive; these are believed to be involved in regulating circadian rhythm (2). RGC axons are the sole output neurons from the eye whose axons form the optic nerve, optic chiasm and optic tract. RGCs are an important model system in developmental neurobiological research, particularly in the areas of axon guidance, formation of topographic maps and neural plasticity (7).
Neuronal Type: sensory neuron, interneuron
At least 13 distinct types of retinal ganglion cells (RGCs) can be identified by their dendritic morphologies (3), though some types are better understood than others.
- M-type (also known as alpha or parasol ganglion cells) are believed to be responsible for detecting motion. They have larger cell bodies, and are sensitive to visual stimuli that changes quickly over time (4). M-type cells have larger receptive fields, and are more sensitive to contrast stimuli, than other types of RGCs. This type of RGC responds to stimuli with a transient burst of action potentials (1). M-type cells make up approximately 5% of all RGCs (1).
- P-type (also known as beta or midget ganglion cells) are believed to be responsible for detecting details in vision. They have smaller cell bodies than M-type cells, and are sensitive to high-frequency spatial stimuli (4). P-type cells have smaller receptive fields than M-type cells, are less sensitive to contrast stimuli, and respond to stimuli with a sustained discharge of action potentials as long as the stimulus is present (1). P-type cells make up approximately 90% of the RGC population (1).
- Non-M, non-P type are a diverse group of cell types that make up the remaining 5% of RGCs. Their roles in vision are less understood than M- and P-type ganglion cells, but it is known that some non-M, non-P type cells are involved in color vision (1).
- Photoreceptive ganglion cells have a unique role in the visual system. They respond slowly to light stimulus, and maintain a steady signal reflecting the level of light striking the eye. Photoreceptive RGCs "depolarize in response to light by opening cation channels, use an invertebrate-like photopigment (melanopsin), generate action potentials, and connect directly to thalamic and brainstem visual centers. Their primary functional roles relate to non-image-forming visual reflexes, such as circadian entrainment, the pupillary light reflex, and photic regulation of pineal melatonin release" (2).
A summary diagram of retinal ganglion cell types. From a 2003 paper by Dacey, Peterson, Robinson & Gamlin at the University of Washington (3).
- The cell bodies of retinal ganglion cells (RGCs) are located in the ganglion cell layer of the retina, which is located closest to the center of the eye and furthest from the photoreceptor layer on the rear surface of the retina (1).
- RGC axons project across the inner surface of the retina until they meet up at the optic disc. At this point, a bundle of RGC axons exits the eye and is called the optic nerve (cranial nerve II). The optic nerves from both eyes meet at the optic chiasm, where the axons segregate by visual fields. Axons from RGCs in the right visual field of both eyes continue into the left optic tract and on towards the left lateral geniculate nucleus (LGN) of the thalamus. A small number of RGC axons also innvervate the superior colliculus and hypothalamus. Axons from RGCs in the left visual field continue into the right optic tract and corresponding brain structures of the right hemisphere. The entire pathway of RGC axons is often referred to as the retinofugal projection (1).
- There are approximately 1.6 million RGCs in humans, which transmit integrated information from 125 million photoreceptors (5).
Most retinal ganglion cells (RGCs) are glutamatergic, though some have been stained positive for somatostatin and substance P. There is some evidence that a few RGCs may use nitric oxide as a neurotransmitter or neuromodulator (9).
Unique molecular markers
NGF, NSCL2 (10).
PKC, Hu, and Brn3b (11).
Image modified from a 2007 paper by Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, & Kunisada T (PMID 17336960). Panel I shows an H&E staining of the retina, with the ganglion cell layer labeled "GCL." Panels J, K and L show staining for Hu, PKC and Brn3b respectively (11).
Bipolar cells of the retina synapse on retinal ganglion cells (RGCs) in the inner plexiform layer of the retina, and pass on integrated signals from the photoreceptors of the retina. RGCs also make lateral connections with amacrine cells in the inner plexiform layer (1).
The axons of most RGCs synapse in the lateral geniculate nuclei (LGN) of the thalamus, though some synapse in a retinotopic fashion in the superior colliculus, and others synapse in the hypothalamus (1). M-type ganglion cells synapse in the magnocellular LGN layers, P-type ganglion cells synapse in the parvocellular LGN layers, and non-M non-P ganglion cells synapse in the koniocellular layers of the LGN (5).
Retinal ganglion cells (RCGs) are organized in concentric center-surround receptive fields. The center of the receptive field can be of two types: ON-center and OFF-center. ON-center ganglion cells depolarize in response to light striking the center areas of the receptive fields, while OFF-center ganglion cells respond to a dark spot on the center of their receptive fields. However, in both cases, the response is inhibited by a stimulus in the surround area (1). P-type and non-M non-P type RGCs are often arranged in center-surround receptive fields that respond to two opposing colors rather than simple light and dark stimuli (1). Because of these properties, RGCs respond better to boundary conditions than to uniform fields of light or color.
Axons from developing retinal ganglion cells (RGCs) have to grow in a very particular pattern to the correct area of the brain. Because of the easier access to the retina for studies, and because of the length of the path that the developing axons must travel, RGCs have been an intensely studied model of axon pathfinding. Their axons must join together (fasciculate), leave the eye in a bundle, join with a bundle of axons from the other eye at the optic chiasm, and continue on to specific targets in the brain (6). A number of molecular signaling pathways have been identified in RGC axon pathfinding , including L1 (a member of the immunoglobin family of cell adhesion molecules), netrin-1 (a secreted attractant), chondroitin sulphate proteoglycan (an inhibitory cell matrix molecule), slit proteins (inhibitory proteins), Sema3A (a secreted inhibitor) and the ephrin/Eph-receptor family (membrane bound inhibitors or attractants) (6). The balance and complex interactions of all of these attractants and inhibitors (as well as other, yet undiscovered, factors) guide the developing axon along the correct pathway to its target.
Many sensory and motor functions of the nervous system are arranged topographically, meaning that the order of the neural connections in the space of the brain reflects the position of the sensory stimuli or motor commands. For example, sensory neurons of the cochlea are arranged from low to high frequency, and the organization of the somatosensory cortex is arranged as a representation of the entire body (1). The most studied model for topographic map formation are the connections between RGCs and the superior colliculus. Neurons from the nasal (inner) portion of the retina connect to the caudal (back) end of the superior colliculus and neurons from the temporal (outer) portion of the retina connect to the rostral (front) end, and the spatial relationship between the neurons in the retina is tightly conserved throughout the superior colliculus (7). It is believed that this process is controlled by gradients of ephrins in the superior colliculus which repel opposite gradients of Eph receptors on the RGCs (8).
Model for Neural Plasticity
When parts of either the retina or the superior colliculus are ablated early in development, the retinotectal topographic map formed by the connections of RGC axons to the superior colliculus either expands or compresses to fill the available space, suggesting that the pathways and targets of extending axons are not pre-determined, and providing a model for the study of neural plasticity (7).
The dedication of neurobiology researchers to the study of retinal ganglion cells is embodied in the choice of body art by science blogger Sandra Kiume: an intrinsically photosensitive retinal ganglion cell.
For those interested, there is a video of the actual tattooing process at http://scienceblogs.com/omnibrain/2007/12/multimedia_friday_new_tattoo.php.
(1) Bear, MF, Connors, BW & Paradiso, MA. (2007) Neuroscience: Exploring the Brain. Baltimore, MD: Lippincort.
(2) Wong, KY, Dunn, FA, Berson, DM. (2005) Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells. Neuron 48(6):1001-10. PMID 16364903.
(3) Dacey, DM, Peterson, BB, Robinson, FR & Gamlin, PD. (2003). Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN-projecting ganglion cell types. Neuron 37(1):15-27. PMID 12526769.
(4) Ji, J, So, RH, Lor, FL, Cheung, RT, Howarth, P & Stanney, K. (2005) A search for possible neural pathways leading to visually induced motion sickness. Vision 17(2):131-134.
(5) Callaway EM. (2005). Structure and function of parallel pathways in the primate early visual system. J Physiol. 566(1):13-19 PMID 15905213.
(6) Oster, SF & Sretavan, DW. (2002). Connecting the eye to the brain: the molecular basis of ganlion cell axon guidance. Br. J Ophthalmol. 87:639-645. PMID 12714414.
(7) Lemke, G & Reber, M. (2005). Retinotectal mapping: new insights from molecular genetics. Annu Rev Cell Dev Biol. 21:551-80. PMID 16212507.
(8) Pfeiffenberger, C, Yamada J, & Feldheim DA. (2006). Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system. J Neurosci. 26(50):12873-84. PMID 17167078.
(9) Kolb, H, Fernandez, E & Nelson, R. (2005). Webvision: Neurotransmitters in the retina. Accessed 25 August 2008. URL: http://webvision.med.utah.edu/NT.html.
(10) González-Hoyuela, M, Barbas, J & Rodríguez-Tébar, A. (2001). The autoregulation of retinal ganglion cell number. Development 128:117-124. PMID 11092817.
(11) Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, & Kunisada T. (2007). An in vitro mouse model for retinal ganglion cell replacement therapy using eye-like structures differentiated from ES cells. Exp Eye Res. 84(5):868-75. PMID 17336960.