Role of NMDA receptors in determining function of retinal ganglion cells
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Parallel processing is one of the salient features of visual processing and begins in the retina. In the retina, different circuits culminating in ganglion cells extract various features of a stimulus and process them simultaneously. One way of extracting different information from the same input is by expressing different receptors to sample a particular neurotransmitter. Ganglion cells express AMPA/Kainate and NMDA receptors to sample the glutamatergic input received from bipolar cells. In the first part of this study, I explored the activation of AMPA/Kainate and NMDA receptors in different ganglion cells in the salamander retina. Cells were classified into ON sustained, OFF sustained/transient and ON-OFF transient cells based on their responses to light. NMDA receptors mediate only a small part of the light-evoked synaptic currents under control conditions. Blocking feedback inhibition on bipolar terminals recruited NMDA receptors. This was due to the peri-synaptic localization of NMDA receptors in ON sustained and ON-OFF cells. Comparing the synaptic currents indicated that ON transient responses had a higher NMDA component compared to ON sustained responses. This occurred in spite of both cells expressing a comparable number of NMDA receptors in the postsynaptic membrane. My results implicate a role for release kinetics of bipolar terminals to generate this discrepancy. In the next part of this study, I evaluated the role of AMPA/Kainate and NMDA receptors in determining the spike output of ON transient/sustained ganglion cells. The ability of transient and sustained responses to encode light intensity was determined using three parameters; spike count, maximum spike rate and latency. Transient cells responded at low intensities, and sustained cells responded at relatively higher intensities; hence together they extend the range of intensities the retina can respond to. This is partly due to the higher activation of NMDA receptors in transient cells. In spike count, blocking NMDA receptor activity in transient cells increased the response range but reduced the sensitivity. Hence NMDA receptors increased the sensitivity of the cell at the expense of the range of intensities it can respond to. Blocking NMDA receptors affected the sensitivity of maximum firing rate but not the latency. Hence AMPA/Kainate and NMDA receptors performed different functions in shaping the response of ganglion cells. In the last part, I performed experiments to study an endogenous inhibitory circuit regulating NMDA receptors in ON-OFF cells. The retina expresses three types of inhibitory receptors, and all three types regulate the activation of NMDA receptors directly or indirectly. Glycine receptors had a clear direct effect while the effect of GABAC receptors became apparent after blocking GABAA receptor inhibition. One of the inhibitory pathways, a cross inhibition from the ON pathway to the OFF, regulated NMDA receptor activation. The inhibition through this pathway could be modulated by changing the duration of the stimulus. In summary, I present results in this thesis indicating that relative activation of NMDARs and AMPA/KARs could shape parallel streams of information, and pre-synaptic inhibition can regulate NMDAR activation altering response of the same pathway to different conditions.