Author response: Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses

Abstract From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process1,2. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex3,4, but has not been found in the retina, despite significant effort5,6. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF poly-axonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we found unexpectedly that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a new door to investigation of a novel circuitry that computes motion direction in the primate visual system.

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Direction selectivity in a model of the starburst amacrine cell

Visual Neuroscience ◽

10.1017/s0952523804214109 ◽

2004 ◽

Vol 21 (4) ◽

pp. 611-625 ◽

Cited By ~ 54

Author(s):

JOHN J. TUKKER ◽

W. ROWLAND TAYLOR ◽

ROBERT G. SMITH

Keyword(s):

Amacrine Cell ◽

Dendritic Tree ◽

Sine Wave ◽

Direction Selectivity ◽

Membrane Properties ◽

Calcium Signal ◽

Inhibitory Input ◽

Excitatory Postsynaptic Potential ◽

Global Signal ◽

Starburst Amacrine Cell

The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On–Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when γ-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed “global” signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.

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Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses

eLife ◽

10.7554/elife.42392 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 9

Author(s):

Laura Hanson ◽

Santhosh Sethuramanujam ◽

Geoff deRosenroll ◽

Varsha Jain ◽

Gautam B Awatramani

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Direction Selectivity ◽

Cell Responses ◽

Receptor Knockout Mouse ◽

Starburst Amacrine Cells ◽

Gabaergic Synapses ◽

Novel Strategy ◽

Starburst Amacrine Cell ◽

Differential Connectivity

In the mammalian retina, direction-selectivity is thought to originate in the dendrites of GABAergic/cholinergic starburst amacrine cells, where it is first observed. However, here we demonstrate that direction selectivity in downstream ganglion cells remains remarkably unaffected when starburst dendrites are rendered non-directional, using a novel strategy combining a conditional GABAA α2 receptor knockout mouse with optogenetics. We show that temporal asymmetries between excitation/inhibition, arising from the differential connectivity patterns of starburst cholinergic and GABAergic synapses to ganglion cells, form the basis for a parallel mechanism generating direction selectivity. We further demonstrate that these distinct mechanisms work in a coordinated way to refine direction selectivity as the stimulus crosses the ganglion cell’s receptive field. Thus, precise spatiotemporal patterns of inhibition and excitation that determine directional responses in ganglion cells are shaped by two ‘core’ mechanisms, both arising from distinct specializations of the starburst network.

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Author response: Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

10.7554/elife.34241.034 ◽

2018 ◽

Cited By ~ 1

Author(s):

Thomas A Ray ◽

Suva Roy ◽

Christopher Kozlowski ◽

Jingjing Wang ◽

Jon Cafaro ◽

...

Keyword(s):

Amacrine Cell ◽

Author Response ◽

Starburst Amacrine Cell

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Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses

10.1101/428532 ◽

2018 ◽

Author(s):

Laura Hanson ◽

Santhosh Sethuramanujam ◽

Geoff deRosenroll ◽

Gautam B. Awatramani

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Direction Selectivity ◽

Cell Responses ◽

Receptor Knockout Mouse ◽

Starburst Amacrine Cells ◽

Gabaergic Synapses ◽

Novel Strategy ◽

Starburst Amacrine Cell ◽

Differential Connectivity

SummaryIn the mammalian retina, asymmetric inhibitory signals arising from the direction-selective dendrites of GABAergic/cholinergic starburst amacrine cells are thought to be crucial for originating direction selectivity. Contrary to this notion, however, we found that direction selectivity in downstream ganglion cells remains remarkably unaffected when starburst output is rendered non-directional (using a novel strategy combining a conditional GABAA α2 receptor knockout mouse with optogenetics). We show that temporal asymmetries between excitation/inhibition, arising from the differential connectivity patterns of starburst cholinergic and GABAergic synapses to ganglion cells, form the basis for a parallel mechanism generating direction selectivity. We further demonstrate that these distinct mechanisms work in a coordinated way to refine direction selectivity as the stimulus crosses the ganglion cell’s receptive field. Thus, precise spatiotemporal patterns of inhibition and excitation that shape directional responses in ganglion cells are shaped by two ‘core’ mechanisms, both arising from distinct specializations of the starburst network.

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