Inhibitory control of feature selectivity in an object motion sensitive circuit of the retina

Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond to local movements in a visual scene but remain silent during self-generated global image motion. The excitatory inputs that drive responses of W3-RGCs to local motion were recently characterized, but which inhibitory neurons suppress W3-RGCs’ responses to global motion, how these neurons encode motion information, and how their connections are organized along the excitatory circuit axis remains unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2-AC, exhibits fast responses to global motion and slow responses to local motion. Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type-specific silencing reveals that temporally coded inhibition from TH2-ACs cancels W3-RGC spike responses to global but not local motion stimuli and, thus, controls the feature selectivity of OMS signals sent to the brain

An excitatory amacrine cell detects object motion and provides feature-selective input to ganglion cells in the mouse retina

Retinal circuits detect salient features of the visual world and report them to the brain through spike trains of retinal ganglion cells. The most abundant ganglion cell type in mice, the so-called W3 ganglion cell, selectively responds to movements of small objects. Where and how object motion sensitivity arises in the retina is incompletely understood. In this study, we use 2-photon-guided patch-clamp recordings to characterize responses of vesicular glutamate transporter 3 (VGluT3)-expressing amacrine cells (ACs) to a broad set of visual stimuli. We find that these ACs are object motion sensitive and analyze the synaptic mechanisms underlying this computation. Anatomical circuit reconstructions suggest that VGluT3-expressing ACs form glutamatergic synapses with W3 ganglion cells, and targeted recordings show that the tuning of W3 ganglion cells' excitatory input matches that of VGluT3-expressing ACs' responses. Synaptic excitation of W3 ganglion cells is diminished, and responses to object motion are suppressed in mice lacking VGluT3. Object motion, thus, is first detected by VGluT3-expressing ACs, which provide feature-selective excitatory input to W3 ganglion cells. DOI: http://dx.doi.org/10.7554/eLife.08025.00

Motion processing in the mouse retina

Recognizing object motion is one of the essential visual functions for survival. Object motion information is first detected by the retina. Among approximately 30 different types of retinal ganglion cells (RGCs), some motion detecting RGCs (e.g. direction-selectivity, differential motion detection, edge detection) have been identified. However, except for the direction-selective retinal circuit, specific circuit components and underlying mechanisms of motion information processing in the retina are poorly understood. Recent findings show amacrine cells (ACs), inhibitory interneurons in the inner retina, often determine response properties of retinal outputs (e.g. direction selectivity). ACs are the most diverse neuronal class in the retina yet only a few types are thoroughly studied. Studying characteristics of specific AC types and their functional roles in the circuit is crucial to understanding how the retina processes object motion information. The second chapter of my thesis focuses on one type of AC, the VG3-AC, which expresses vesicular glutamate transporter 3 (VGluT3). In order to analyze VG3-ACs’ receptive field properties, I first examined light responses of VG3-ACs in the flat-mounted retina to broad sets of visual stimuli under 2-photon guidance in VGluT3-Cre transgenic mice. My results demonstrate that VG3-ACs detect object motion. Furthermore, I explored the functional role of VG3-ACs in the retinal circuit. The activation pattern of a RGC type called W3-RGC, also known as local edge detecting RGC, exactly corresponded to responses of VG3-ACs. Anatomical reconstruction of the circuit elicited the connectivity between VG3- ACs and W3-RGCs. Then, by comparing wild-type and VGluT3 knock-out mice, I demonstrated that W3-RGCs receive object motion sensitive (OMS) glutamatergic input from VG3-Acs. The fourth chapter of my thesis investigated whether motion processing in the retina can alter visually guided behaviors of the animal. Looming visual stimuli, also called approaching motion visual stimuli, evoke defensive behaviors of the animal. Brain networks that mediate this defensive response have recently been identified. In the retina, however, it is unknown whether a single or multiple neural circuits contribute to encoding looming stimulus detection to drive such a behavior. Recent optogenetic studies demonstrated VG3- ACs connect to several downstream RGCs. W3-RGC and OFFα-RGC are two RGC types considered to receive glutamatergic input from VG3-ACs and to detect looming stimulus. Thus, I tested the responses of VG3-ACs to approaching motion visual stimuli and compared them to the excitatory input W3- and OFFα-RGCs receive. Then, I examined whether removing VG3-ACs in the mature retinal circuit affects responses of W3-RGCs and OFFα - RGCs, and defensive behaviors of the animal. Overall, my thesis work reveals characteristics of the VG3-AC type, contributions of VG3-AC in motion information processing in retinal circuits and in animal’s defensive behavior, and underlying synaptic mechanisms of VG3-ACs in an aspect of their feature-selectively tuned excitatory input to downstream partners

Target-Specific Glycinergic Transmission from VGluT3-Expressing Amacrine Cells Shapes Suppressive Contrast Responses in the Retina

Summary: Neurons that release more than one transmitter exist throughout the CNS. Yet, how these neurons deploy multiple transmitters and shape the function of specific circuits is not well understood. VGluT3-expressing amacrine cells (VG3-ACs) provide glutamatergic input to ganglion cells activated by contrast and motion. Using optogenetics, we find that VG3-ACs provide selective glycinergic input to a retinal ganglion cell type suppressed by contrast and motion (SbC-RGCs). Firing of SbC-RGCs is suppressed at light ON and OFF over a broad range of stimulus sizes. Anatomical circuit reconstructions reveal that VG3-ACs form inhibitory synapses preferentially on processes that link ON and OFF arbors of SbC-RGC dendrites. Removal of VG3-ACs from mature circuits reduces inhibition and attenuates spike suppression of SbC-RGCs in a contrast- and size-selective manner, illustrating the modularity of retinal circuits. VG3-ACs thus use dual transmitters in a target-specific manner and shape suppressive contrast responses in the retina by glycinergic transmission. : Tien et al. show that VG3-ACs deploy dual transmitters (glycine and glutamate) in a target-specific manner and form glycinergic synapses on the link processes connecting ON and OFF arbors of SbC-RGC dendrites. Cell-type-specific deletion in mature circuits reveals contrast- and size-selective influences of VG3-ACs on SbC-RGC responses