Ornithine Decarboxylase

Supplementary Materials1: Supplemental Movie 1: Dendritic origin of spike signature differences, Related to Physique 5 The electrical image over time of the two distinct SM cell signature clusters shown in Fig

Supplementary Materials1: Supplemental Movie 1: Dendritic origin of spike signature differences, Related to Physique 5 The electrical image over time of the two distinct SM cell signature clusters shown in Fig. types in primates, and the parallel visual pathways they initiate, remain poorly understood. Here, unusual physiological and computational properties of the ON and OFF easy monostratified ganglion cells are explored. Large-scale multi-electrode recordings from 48 macaque retinas revealed that these cells exhibit irregular receptive field structure composed of spatially segregated hotspots, quite different from the classical center-surround model of retinal receptive fields. Surprisingly, visual stimulation of different hotspots in the same cell produced spikes with subtly different spatiotemporal voltage signatures, consistent with a dendritic contribution to hotspot structure. Targeted visual stimulation and computational inference exhibited strong nonlinear subunit properties associated with each hotspot, supporting a model in which the hotspots apply nonlinearities at a larger spatial scale than bipolar cells. These findings reveal a previously unreported nonlinear mechanism in the output of the primate retina that contributes to signaling spatial information. eTOC Blurb Rhoades et al. find the easy monostratified retinal ganglion cells in the primate retina have unusual receptive fields consisting of multiple hotspots. This differs from classical center-surround receptive field models and suggests a role in nonlinear visual computation. Introduction A diverse collection of retinal ganglion cell (RGC) types extracts features of the visual scene and transmits the results to various targets in the brain. Each RGC type exhibits characteristic light responses, connects to specific retinal interneuron types, and covers the entire visual field, forming a distinct channel of information. Work in mice and other species has begun to reveal the diverse computations performed by the various RGC types, and their relationship to visual behaviors (Gollisch and Meister, 2010; Masland, 2001; Rodieck, 1998; W?ssle, 2004). However, in the primate retina, despite a nearly complete anatomical catalog of roughly 20 RGC types, understanding of their distinct visual computations and underlying cellular and circuit properties remains limited (Dacey et al., 2003; Masri et al., 2019; Yamada et al., 2005). Most physiological studies have been performed around the five numerically dominant RGC types: ON and OFF midget (Dacey, 1993), ON and OFF parasol (Chichilnisky and Kalmar, 2002), and small bistratified (Field et al., 2007). These cells are usually characterized as exhibiting classical Gaussian center-surround receptive field (RF) structure, with relatively little evidence for specialized functional properties such as those found in mouse RGCs (Crook et al., 2008; Enroth-Cugell and Robson, 1966; Kuffler, 1953; Rodieck, 1998; but see Manookin et al., 2018). The function of visual signaling in the remaining low-density RGC types remains largely unknown (Puller et al., 2015), and the anatomical homology of RGC types between rodents and IWP-L6 primates is usually far from clear (Roska and Meister 2014; Peng et al., 2019). Thus, it is uncertain whether the low-density RGC types in primates could serve distinctive roles in vision based on unique physiological mechanisms, as is the case in other species. A primary reason for this limited understanding is the technical challenge of recording from low-density RGC types in primate, each of which constitute only a few percent of the total population (Dacey et al., 2003; Yamada et al., 2005). Here we combine large-scale multi-electrode recording with single-cell patch recording to explore the properties of two low-density RGC types: the ON and OFF easy monostratified (SM) cells (Crook et al., 2008). These two cell types exhibited unusually irregular RFs with multiple distinct hotspots of light sensitivity. An unexpected spike generation mechanism produced distinct spatio-temporal spike voltage signatures in a given RGC. Closed-loop visual stimulation and computational inference revealed that this hotspots behave as nonlinear subunits that are larger and more spatially segregated than those found in other cell types, potentially allowing selectivity for different spatial features than the well-known bipolar cell subunits. Results Receptive field properties of simultaneously recorded retinal ganglion cell types To explore the properties of low-density RGC types, large-scale multi-electrode recordings were used to simultaneously record the light responses of hundreds of RGCs (Chichilnisky and Kalmar, 2002; Field et al., 2010; Frechette et al., 2005; Litke et al., 2004). The spatial, temporal, and chromatic response properties of each recorded RGC were examined by computing the reverse correlation between its spike train IWP-L6 and a spatiotemporal noise stimulus. The resulting spike-triggered average (STA) stimulus captures the spatial RF, time course, and chromatic properties of each cell analyzed (Fig. 1; Chichilnisky, Rock2 2001). To distinguish cell types, the RF area and first principal component of the STA time course IWP-L6 were examined (Fig. 1A). As previously exhibited (Field et al., 2007), the five major high-density cell type can be readily identified based on these.