A Dendrite-Autonomous Mechanism for Direction Selectivity in Retinal Starburst Amacrine Cells

Abstract

Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca²⁺ signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca²⁺] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage–activated Ca²⁺ channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination. The visual system dedicates substantial resources to detecting motion and its direction. For more than 40 years, researchers have tried to decipher the underlying computational mechanisms by which retinal neurons compute directed motion. One type of retinal interneuron involved in direction discrimination is the “starburst” amacrine cell. Starburst-cell dendrites are strongly activated by visual motion from their somata towards the dendritic tips, but not by motion in the opposite direction. It has been proposed, for example, that directional selectivity arises from lateral inhibitory interactions in which activated cells inhibit their neighbors. However, despite extensive modeling, the underlying physiological mechanism has remained elusive. Here, by combining whole-cell recordings, two-photon microscopy, and modeling, we show that discrimination of motion direction in starburst-cell dendrites does not require lateral inhibitory interactions in the retina, but can be generated by a “dendrite-autonomous” computation, which relies on intrinsic electrical mechanisms. Blocking inhibitory interactions does not eliminate directional responses, whereas differential activation of voltage-gated membrane conductances and a dendritic voltage gradient can provide the necessary spatial asymmetry to produce directional signals. The computation underlying dendrite-autonomous direction selectivity may represent one of the most intricate examples to date of dendritic information processing.