Gain control by sparse, ultra-slow glycinergic synapses

Jain, Varsha; Hanson, Laura K.; Sethuramanujam, Santhosh; Michaels, Tracy; Gawley, Jerram; Gregg, Ronald G.; Pyle, Ian Scott; Zhang, Chi; Smith, Robert G.; Berson, David M.; McCall, Maureen A.; Awatramani, Gautam B.

doi:10.1016/j.celrep.2022.110410

Cited by 12 publications

(15 citation statements)

References 51 publications

(108 reference statements)

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“…Two were synapses from Type H18 amacrine cells [25, 26] and one was from an unidentified medium-field type. We detected no synaptic inputs from any of the many other types of small-field amacrine cell types, even after examining a large sample of such cells reconstructed in another study [26]. We conclude that VGluT3 amacrine cells are by far the best candidate glycinergic cell type shaping the slow-speed tuning of ON DSGCs.…”

Section: Resultsmentioning

confidence: 99%

“…To our surprise, nearly all of them appeared to be VGluT3 amacrine cells, as documented below (n=38 synapses from 16 cells). Two were synapses from Type H18 amacrine cells [25, 26] and one was from an unidentified medium-field type. We detected no synaptic inputs from any of the many other types of small-field amacrine cell types, even after examining a large sample of such cells reconstructed in another study [26].…”

Section: Resultsmentioning

confidence: 99%

“…This may indicate that there are other sources of glycinergic input. The connectomic analysis did identify two synapses from H18 amacrine cells [25,46] to ON DSGCs. If H18 cells are glycinergic, as suggested by their relatively small, highly branched dendritic arbors, their contributions to ON DSGC inhibition would have been blocked by strychnine but not by our chemogenetic manipulation.…”

Section: Are Vglut3 Cells the Sole Source Of Glycinergic Inhibition O...mentioning

confidence: 99%

Section: Electron Microscopic Reconstructions Identify Vglut3 Amacrin...mentioning

confidence: 99%

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A retinal circuit that vetoes optokinetic responses to fast visual motion

Mani

Yang

Zhao

et al. 2021

Preprint

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Optokinetic nystagmus (OKN) is a visuomotor reflex that works in tandem with the vestibulo-ocular reflex (VOR) to stabilize the retinal image during self-motion. OKN requires information about both the direction and speed of retinal image motion. Both components are computed within the retina because they are already encoded in the spike trains of the specific class of retinal output neurons that drives OKN ─ the ON direction-selective ganglion cells (ON DSGCs). The synaptic circuits that shape the directional tuning of ON DSGCs, anchored by starburst amacrine cells, are largely established. By contrast, little is known about the cells and circuits that account for the slow speed preference of ON DSGCs and, thus, of OKN that they drive. A recent study in rabbit retina implicates feedforward glycinergic inhibition as the key suppressor of ON DSGC responses to fast motion. Here, we used serial-section electron microscopy, patch recording, pharmacology, and optogenetic and chemogenetic manipulations to probe this circuit in mouse retina. We confirm a central role for feedforward glycinergic inhibition onto ON DSGCs and identify a surprising primary source for this inhibition ─ the VGluT3 amacrine cell (VG3 cell). VG3 cells are retinal interneurons that release both glycine and glutamate, exciting some neurons and inhibiting others. Their role in suppressing the response of ON DSGCs to rapid global motion is surprising. VG3 cells had been thought to provide glutamatergic excitation to ON-DSGCs, not glycinergic inhibition, and because they have strong receptive fields surrounds which might have been expected to render them unresponsive to global motion. In fact, VG3 cells are robustly activated by the sorts of fast global motion that suppress ON DSGCs and weaken optokinetic responses as revealed by dendritic Ca+2 imaging, since surround suppression is less prominent when probed with moving gratings than with spots. VG3 cells excite many ganglion cell types through their release of glutatmate. We confirmed that for one such type, the ON-OFF DSGCs, VG3 cells enhance the response to fast motion in these cells, just as they suppress it in ON DSGCs. Together, our results assign a novel function to VGluT3 cells in shaping the velocity range over which retinal slip drives compensatory image stabilizing eye movements. In addition, fast speed motion signal from VGluT3 cells is used by ON-OFF DSGCs to extend the speed range over which they respond, and might be used to shape the speed tuning or temporal bandwidth of the responses of other RGCs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Are Vglut3 Cells the Sole Source Of Glycinergic Inhibition O...mentioning

confidence: 99%

Section: Electron Microscopic Reconstructions Identify Vglut3 Amacrin...mentioning

confidence: 99%

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A retinal circuit that vetoes optokinetic responses to fast visual motion

Mani

Yang

Zhao

et al. 2021

Preprint

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“…GABA release by starburst dendrites inhibits neighboring starburst cells in mouse and rabbit, generating positive feedback and disinhibition (Lee & Zhou, 2006; Chen et al, 2016; Ding et al, 2016; Morrie & Feller, 2018; Chen et al, 2020). Glycine released by narrow-field amacrine cells in mouse retina is a potent inhibitory modulator of starburst EPSP amplitude and contrast gain (Jain et al, 2022). Further, the nonlinear voltage activation of calcium channels in starburst dendrites can modify the DS for neurotransmitter release (Tukker et al, 2004), and calcium channel activation can regeneratively amplify the directional EPSP signals (Fig.…”

Section: Discussionmentioning

confidence: 99%

Two mechanisms for direction selectivity in a model of the primate starburst amacrine cell

et al. 2023

Self Cite

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In a recent study, visual signals were recorded for the first time in starburst amacrine cells of the macaque retina, and, as for mouse and rabbit, a directional bias observed in calcium signals was recorded from near the dendritic tips. Stimulus motion from the soma toward the tip generated a larger calcium signal than motion from the tip toward the soma. Two mechanisms affecting the spatiotemporal summation of excitatory postsynaptic currents have been proposed to contribute to directional signaling at the dendritic tips of starbursts: (1) a “morphological” mechanism in which electrotonic propagation of excitatory synaptic currents along a dendrite sums bipolar cell inputs at the dendritic tip preferentially for stimulus motion in the centrifugal direction; (2) a “space–time” mechanism that relies on differences in the time-courses of proximal and distal bipolar cell inputs to favor centrifugal stimulus motion. To explore the contributions of these two mechanisms in the primate, we developed a realistic computational model based on connectomic reconstruction of a macaque starburst cell and the distribution of its synaptic inputs from sustained and transient bipolar cell types. Our model suggests that both mechanisms can initiate direction selectivity in starburst dendrites, but their contributions differ depending on the spatiotemporal properties of the stimulus. Specifically, the morphological mechanism dominates when small visual objects are moving at high velocities, and the space–time mechanism contributes most for large visual objects moving at low velocities.

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Distinct inhibitory pathways control velocity and directional tuning in the mouse retina

Summers

Feller

2022

Current Biology

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Gain control by sparse, ultra-slow glycinergic synapses

Cited by 12 publications

References 51 publications

A retinal circuit that vetoes optokinetic responses to fast visual motion

A retinal circuit that vetoes optokinetic responses to fast visual motion

Two mechanisms for direction selectivity in a model of the primate starburst amacrine cell

Distinct inhibitory pathways control velocity and directional tuning in the mouse retina

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