Mechanisms of direction selectivity in starburst amacrine cells

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For the brain to detect relevant signals about the outside world, neurons must be able to collect, manipulate and transmit information. Detecting motion is a fundamental task of the visual system, and specialized direction selective (DS) cells are present already at the retina. Due to its experimental accessibility, the DS circuit in the mammalian retina emerged as a classical model system of a sophisticated information processing in the brain. Retinal DS ganglion cells are maximally activated by motion in their preferred direction, and their output guides reflexive behavior and possibly conscious perception. It is now well established that directional tuning of the ganglion cells reflects DS input from starburst amacrine cells (SAC), where the first fundamental step of motion detection takes place. SAC dendrites transform a non-DS input from bipolar cells into DS output that is manifested as a stronger output for motion in the outward direction. A rich literature indicates that DS in individual SACs depends on an intricate combination of factors, including dendritic morphology, dynamics of the synaptic inputs and the distribution of voltage-gated channels. While a number of different mechanisms have been proposed to explain the transformation of visual information from unselective inputs into direction selective output, the relative contribution of these processes to the function of the cell remains controversial. In addition, detailed numerical simulations that incorporate the leading models of DS in SACs underestimate the experimentally recorded motion discrimination abilities in these cells, indicating the presence of additional unidentified DS mechanism(s). The goal of this proposal is to address the mechanisms that mediate DS in individual SACs. We will take an innovative approach that combines biophysically realistic modeling, electrophysiology, as well as glutamate and calcium imaging to provide a detailed description of the of the visual information representation in the DS circuit, with a particular focus on SAC dendrites. The proposed experimental and theoretical treatment will study how visual signals are transformed to synaptic inputs that innervate SACs and test a novel mechanism that depends on postsynaptic voltage-gated channels to sharpen DS signals in SAC dendrites. The proposed research will substantially advance our understanding of DS mechanisms in the visual system. It will also provide a conceptually novel role for the participation of active channels in dendritic computations.