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

SHORT REPORT elifesciences.org An excitatory amacrine cell detects object motion and provides feature-selective input to ganglion cells in the mouse retina Tahnbee Kim1,2, Florentina Soto1, Daniel Kerschensteiner1,3,4* 1 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States; 2Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, United States; 3Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, United States; 4Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, United States Abstract 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 socalled 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-photonguided 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. *For correspondence: Competing interests: The authors declare that no competing interests exist. Funding: See page 13 Received: 10 April 2015 Accepted: 18 May 2015 Published: 19 May 2015 Reviewing editor: Alexander Borst, Max Planck Institute of Neurobiology, Germany Copyright Kim et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. DOI: 10.7554/eLife.08025.001 Introduction A diverse array of circuits in the retina processes signals from photoreceptors and parses information into spike trains of 20–30 types of retinal ganglion cells (RGCs), each encoding distinct aspects of the visual scene (Masland, 2012). The most abundant RGC type in the mouse retina (W3RGC) was recently shown to respond selectively to movements of small—in terms of size on the retina—objects (Zhang et al., 2012). Detecting object motion is a challenging task as head, body, and eye movements frequently shift the retinal image (Martinez-Conde et al., 2004; Sakatani and Isa, 2007). To distinguish movements of objects and the background, object motion sensitive (OMS) RGCs respond to differences in the timing of texture movements in their receptive field center and surround (Olveczky et al., 2003; Zhang et al., 2012). W3-RGCs share key properties with OMS RGCs in rabbit and salamander, but, due to stronger surround suppression, do not respond at the border of larger objects (Zhang et al., 2012). This feature is reminiscent of localedge-detector RGCs described in several species (Levick, 1967; Zeck et al., 2005; Roska et al., 2006). W3-RGCs, thus, appear to be in the intersection of OMS and local-edge-detector RGCs. Although postsynaptic inhibition and spike thresholds sharpen the tuning of W3-RGCs, similar to other OMS and local-edge-detector RGCs, key response properties appear to be inherited from their excitatory input (van Wyk et al., 2006; Baccus et al., 2008; Russell and Werblin, 2010; Kim et al. eLife 2015;4:e08025. DOI: 10.7554/eLife.08025 1 of 15 Short report Neuroscience eLife digest Animals can use their eyes to detect moving objects, which helps them to avoid predators and other threats, and to spot potential prey or allies. Visual information from the eyes is sent to the brain, which processes the information to form a coherent picture of how the objects are moving. This processing has to be able to account for movements of the head, eyes, and body—which can cause the image of an object on the retina within the eye to move even if the object itself remains stationary. Within the retina, light is converted into electrical signals by cells called rods and cones. A layer of cells called bipolar cells relay these signals to the ‘ganglion’ cells, which in turn pass them on to the brain. In mice, a type of ganglion cell called the W3 ganglion cell has been shown to respond selectively to small moving objects, but exactly how these cells acquire their motion sensitivity remained unclear. Kim et al. now reveal that cells called amacrine cells, which regulate the transfer of signals from the bipolar cells to ganglion cells, supply the information needed for motion detection. The mouse eye contains up to 50 different types of amacrine cells. One of these—called the VG3-amacrine cell—increases its activity whenever an object moves relative to its background, but decreases its activity whenever the object and background move together. The overall effect is that the cells respond selectively to the presence of small moving objects. Most amacrine cells regulate the transfer of signals within the retina by inhibiting the activity of ganglion cells. But, Kim et al. show that VG3-amacrine cells release a molecule called glutamate to activate W3 ganglion cells when a moving object is detected. These unusual and specialized cells are, thus, an essential component of a circuit in the nervous system that supports motion detection. It is possible that some other types of amacrine cells may also play specialized roles in the detection of other features in the visual world. DOI: 10.7554/eLife.08025.002 Zhang et al., 2012). This suggests that feature selectivity arises presynaptic to W3-RGCs. Where and how object motion is first detected remains to be determined. Typically, RGCs receive excitatory input from bipolar cells (Euler et al., 2014) and inhibitory input from amacrine cells (ACs). ACs are the most diverse class of neurons in the retina, encompassing 30–50 cell types (MacNeil and Masland, 1998; Helmstaedter et al., 2013) that serve task-specific functions in vision (Dacheux and Raviola, 1986; Yoshida et al., 2001; Euler et al., 2002; Munch et al., 2009; Grimes et al., 2010; Chen and Li, 2012). Although most ACs release γ-Aminobutyric acid (GABA) or glycine, a wide range of neurotransmitters and neuromodulators can be found in different cell types including one expressing the vesicular glutamate transporter 3 (VGluT3) (gene: Slc17a8, protein: VGluT3, AC: VG3) (Fyk-Kolodziej et al., 2004; Haverkamp and Wassle, 2004; Jo (...truncated)