Mechanisms of Synaptic Processing in the Retina

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DESCRIPTION (provided by applicant): How the brain resolves the direction of external motion from the pattern of light passing across the retina has puzzled neuroscientists for decades. Neurons that encode the direction of image motion are first encountered in the retina. The neurons are the on-off direction-selective ganglion cells (DSGCs). We will examine in isolation the convergent synaptic mechanisms that generate direction selectivity, and determine how they arise, and how they are integrated by the DSGC. Comparison of the results obtained from this system, with those in other brain regions and other species, will provide new insights into how neural circuits remove redundant information, and extract specific features or patterns from the barrage of incoming synaptic activity. Each DSGC determines the direction of image motion in a small region of visual space. These cells are most selective for movement along a preferred-null axis. Their responses are largest for movement in the preferred direction and smallest for movement in the opposite, null direction. Our preliminary recordings indicate that a mix of synaptic mechanisms generate direction-selective responses. The excitatory and inhibitory inputs to DSGCs are directional, indicating that there is presynaptic modulation of neurotransmitter release from interneurons. Directional responses are also generated within the dendrites of the DSGC, and arise from the postsynaptic integration of excitatory and inhibitory synaptic inputs. A striking finding is that the two distinct dendritic arbors of DSGCs use different synaptic mechanisms to generate a directional signal. The proposed research will use whole-cell patch-clamp recording techniques to analyse the visually evoked synaptic responses in DSGCs in an in vitro rabbit retina preparation. The first aim will determine the origin and nature of the lateral inhibition that is critical for generating direction-selective responses. The second aim will be to determine the synaptic mechanisms that generate directional excitatory inputs to the DSGCs. The third aim will further test the hypothesis that the two dendritic strata generate directional signals using different synaptic mechanisms.