NMDA receptors retina

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Chen S, Diamond JS. 2002. Synaptically released glutamate activates extrasynap-tic NMDA receptors on cells in the ganglion cell layer of rat retina. J. Neurosci. 22(6) 2165-73... 

Retinal circuitry is further refined by ehminating inappropriate synapses. Glutamate, through NMDA receptors, is known to be involved in synaptic pruning in the CNS, and there is evidence that it also does so in the retina. 

NO is an important neuromodulator in the retina, and is implicated in many physiological processes (Goldstein et al., 1996). NO is synthesized from arginine via the action of nitric oxide synthase (NOS). Three distinct isoforms of NOS have been identified. Neuronal NOS (nNOS) and endothelial NOS (eNOS) are Ca -dependent. nNOS is constitutively expressed by certain types of amacrine cells in the retina. These cells often have long projections in the irmerplexiform layer (Sharma et al., 1997 Sharma et al., 2001). eNOS is expressed by the endothelial cells of blood vessels (Cheon et al., 2003). iNOS is Ca -independent and expressed in Muller and RPE cells in response to certain stimuli (Lopez-Costa et al., 1997). Activation of the NMDA receptor leads to an increase in intracellular calcium levels, which can induce expression of, and activate NOS isoforms, either directly (nNOS) or via the activation of calcium-dependent protein kinase C (PKC) (Lipton, 1999) (O Figure 3-6). 

Glutamate s role as a neurotransmitter in the vertebrate retina is reviewed by Barnstable (1993), Brandstatter et al. (1998) and Lo et al. (1998). As the cell bodies of different retinal cell types are in different laminae (Fig. 10), we can assign which general cell types express which glutamate receptor subunits. However, there are different subsets of the same cell class, e.g., there are at least 10 different types of on- and off-bipolars, and multiple subtypes of the other cell classes (Stevens, 1998). Without cell-type markers and double-labelling studies, ISH can not differentiate these. The cones and rods release glutamate onto the bipolar cells only off-bipolars use ionotropic receptors at this synapse on-bipolars use the metabotropic receptor mGluR6 instead. The distribution of NMDA and non-NMDA receptor mRNAs in the retina is summarized in Fig. 10. 

Hartveit E, Brandstiitter JH, Sassoe-Pognetto M, Laurie DJ, Seeburg PH, Wassle H (1994) Localization and developmental expression of the NMDA receptor subunit NR2A in the mammalian retina. J Comp Neurol 348 57-582. 

Watanabe M, Mishina M, Inoue Y (1994e) Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina. Brain Res 634 328-332. 

Retinal ganglion cells are the output cells of the retina. Their axons course along the vitreal surface of the retina and bundle together to exit the eye as the optic nerve. Ganglion cells are excited by glutamate released from bipolar cells acting on both NMDA and non-NMDA (KA- and AMPA-type) glutamate receptors (Thoreson and Witkovsky, 1999). 

Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur J Neurosci 6 1100-1112. 

Fig. 10. The cell types in the rat retina and their expression of the AMPA, NMDA and kainate receptor subunit mRNAs (circuit diagram adapted from Barnstable, 1993 Bahn and Wisden, 1997). The assignment of subunit groupings to different cell classes does not imply that, for example, all amacrine cells co-express all the listed subunits subsets of amacrine cells, horizontal or ganglion cells express different subunit combinations (see text).

Goebel DJ, Aurelia JL, Tai Q, Jojich L, Poosch MS (1998) Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina. Brain Res S0S 141-154. 

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