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.

Chromatic Bipolar Cell Pathways in the Mouse Retina

“…Data were analyzed using Fourier analysis (cf. Hausselt et al, 2007). We took the voltage trace during the sinusoidal light stimulation, discarded the first second (to avoid initial transients) (see Fig.…”

Synchrony Makes Neurons Fire in Sequence, and Stimulus Properties Determine Who Is Ahead

“…There is ample evidence that neurons are highly sensitive coincidence detectors and can distinguish between precisely coinciding and temporally dispersed inputs (Bi and Poo, 1998;Usrey et al, 2000;Ahissar and Arieli, 2001;Azouz and Gray, 2003;London and Häusser, 2005;VanRullen et al, 2005;Meliza and Dan, 2006;Fries et al, 2007;Hausselt et al, 2007;Tsubo et al, 2007;Cardin et al, 2009;Branco et al, 2010). By switching positions in the firing sequence, the inputs to target cells can either coincide or disperse in time, and in the case of dispersion, the sequence can change.…”

“…By switching positions in the firing sequence, the inputs to target cells can either coincide or disperse in time, and in the case of dispersion, the sequence can change. This, too, is a relevant variable for postsynaptic activity, because it matters whether EPSPs at distal dendritic compartments are generated before or after those at proximal sites (London and Häusser, 2005;Hausselt et al, 2007;Branco et al, 2010) (supplemental Fig. S11 F, G, and supplemental Discussion 2, available at www.jneurosci.org as supplemental material).…”

“…Cortical neurons contain an arsenal of cellular mechanisms sensitive to the precise timing of inputs (Bi and Poo, 1998;Usrey et al, 2000;Ahissar and Arieli, 2001;Azouz and Gray, 2003;Meliza and Dan, 2006;Fries et al, 2007;Hausselt et al, 2007;Cardin et al, 2009;Branco et al, 2010). However, it is unclear whether such mechanisms are actually exploited (i.e., whether the fine temporal structure of cortical activity reflects features of the environment).…”

Cellular Inhibitory Behavior Underlying the Formation of Retinal Direction Selectivity in the Starburst Network

“…Further, it has demonstrated that direction selectivity originates in complex subcellular interactions between the dendrites of starburst amacrine cells (SACs) arrayed in a laminar fashion around the directionally selective ganglion cells (DSGCs). The design of the underlying retinal circuitry is understood in broad terms [124,125], but it is still not clearly understood how the directionally selective signal is actually computed [33,48].…”