Neural circuits and synapses for early stage visual processing

Ganglion cells are the output neurons of the retina and send visual information through the optic nerve to various targets in the brain. There are ∼20 types of ganglion cell, and most types encode contrast, the variance in light intensity around the mean level. This thesis investigates how retinal circuits and synapses encode contrast. At the first level of light processing, cone photoreceptors release glutamate onto ON and OFF bipolar cells, which respond to objects brighter or darker than the background and release glutamate onto the corresponding type of ganglion cell. This thesis demonstrates how excitatory and inhibitory synapses work in concert to encode light information in three ganglion cell types: ON Alpha, OFF Alpha, and OFF Delta cells.;First, I demonstrate that excitatory synapses adapt following prolonged stimulation. Following a switch from high to low contrast, a ganglion cell rapidly decreases its responsiveness and recovers slowly over several seconds. This slow adaptation arises from reduced glutamate release from presynaptic bipolar cells. Glutamate released from bipolar cells binds to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors on ganglion cell dendrites. NMDA-mediated responses were present in multiple ganglion cell types but absent in one type, the ON Alpha cell. OFF Alpha and Delta cells used NMDA receptors for encoding different contrast ranges: the full range (Alpha), including near-threshold responses, versus a high range (Delta). The Delta cell expresses the NR2B subunit, consistent with an extra-synaptic NMDA receptor location that is activated by glutamate spillover during high contrast stimulation. The contrast-independent role for NMDA receptors in OFF Alpha cells correlated with two circuit properties: high contrast sensitivity and low presynaptic basal glutamate release.;In addition to excitatory glutamate synapses, OFF ganglion cells are driven by the removal of synaptic inhibition (disinhibition). Experiments implicate the All amacrine cell, better known for its role in rod vision, as a critical circuit element through the following pathway: cone → ON cone bipolar cell → All cell → OFF ganglion cell. These results show a new role for disinhibition in the retina and suggest a new role for the All amacrine cell in daylight vision.