Local Retinal Circuits of Melanopsin-Containing Ganglion Cells Identified by Transsynaptic Viral Tracing

Abstract

Intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) control important physiological processes, including the circadian rhythm, the pupillary reflex, and the suppression of locomotor behavior (reviewed in [1]). ipRGCs are also activated by classical photoreceptors, the rods and cones, through local retinal circuits [2, 3]. ipRGCs can be transsynaptically labeled through the pupillary-reflex circuit with the derivatives of the Bartha strain of the alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6-12]. Bartha-strain derivatives spread only in the retrograde direction [13]. There is evidence that infected cells function normally for a while during GFP expression [7]. Here we combine transsynaptic PRV labeling, two-photon laser microscopy, and electrophysiological techniques to trace the local circuit of different ipRGC subtypes in the mouse retina and record light-evoked activity from the transsynaptically labeled ganglion cells. First, we show that ipRGCs are connected by monostratified amacrine cells that provide strong inhibition from classical-photoreceptor-driven circuits. Second, we show evidence that dopaminergic interplexiform cells are synaptically connected to ipRGCs. The latter finding provides a circuitry link between light-dark adaptation and ipRGC function.

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

“…This rule is occasionally broken, however, as in the case of the infection of RMS cells. In addition, Muller glial infection has been shown for PRV (42), and RABV has been shown to sometimes infect cortical glia (43). VSV(LCMV-G), PRV, and RABV are thus not exclusively transsynaptic.…”

Rod and Cone Contributions to Horizontal Cell Light Responses in the Mouse Retina

“…not clear whether the synaptic contacts are made by the axon terminals or the somata (Viney et al, 2007). Our data suggest that horizontal cell axon terminals receive cone signals from the horizontal cell somata; axon terminals therefore receive a mixture of rod and cone signals.…”

Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells

“…In addition to their intrinsic photosensitivity, melanopsin-expressing RGCs receive synaptic input from retinal bipolar and amacrine cells (Belenky et al, 2003;Dacey et al, 2005;Perez-Leon et al, 2006;Ostergaard et al, 2007;Viney et al, 2007;Wong et al, 2007), and may be electrically coupled to other inner retinal neurons via gap junctions (Sekaran et al, 2003). Isolating ipRGCs into enriched cultures therefore eliminates all extrinsic modulatory influences on the intrinsic light responses that occur in the intact retina, and negates the need for pharmacological blockade of synaptic activity.…”