Retinal projections in mice with inherited retinal degeneration: Implications for circadian photoentrainment

Abstract

The availability of naturally occurring and transgenic retinal mutants has made the mouse an attractive experimental model to address questions regarding photoentrainment of circadian rhythms. However, very little is known about the retinal cells and the retinal projections to the nuclei of the murine circadian timing system. Furthermore, the effect of inherited retinal degeneration on these projections is not understood. In this report, we have used pseudorabies virus as a neuroanatomical tract tracer in mice to address a series of questions: Which retinal cells mediate circadian responses to light? What is the nature of the retinohypothalamic projection? What is the impact of the inherited retinal disorder, retinal degenerate (rd/rd), on the structures of the photoentrainment pathway? Our results show that a class ofretinal ganglion cell, morphologically similar to the type III ganglion cells of the rat, appears to project to central circadian structures of the mouse. They are few in number and sparsely distributed throughout the retina. The low number and broad distribution of these specialized retinal ganglion cells may be an adaptive mechanism to integrate environmental irradiance without compromising the spatial resolution required for vision. In addition, viral infection of conelike and rodlike photoreceptors and amacrinelike cells suggest that these cells may mediate or contribute to circadian responses to light. Inherited retinal degeneration has no obvious effect on the anatomy of the retinal cells or their projections to the circadian axis. These anatomical findings are consistent with our previous findings showing that aged rd/rd mice are capable of regulating their circadian rhythms by light with unattenuated sensitivity.

Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits

“…Typically, PRV infects the CNS by invading neurons in the periphery and then replicating and spreading to the CNS via synaptically linked neurons. However, PRV can also invade neurons through their somata if the viral concentration is sufficient (6), as evidenced by primary infection of retinal ganglion cells (RGCs) after intravitreal injection of PRV (7)(8)(9). Infection of RGCs with PRV-Bartha, followed by viral replication, results in the anterograde transsynaptic infection of a restricted set of retinorecipient neurons [i.e., suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), pretectum (PT), and lateral terminal nucleus].…”

“…1 and 2). Components of the primary visual system (i.e., dorsal lateral geniculate nucleus and superior colliculus) were not labeled after intraocular PRV 152 injection in the hamster, similar to findings after intraocular PRV-Bartha injection in the rat and mouse (7)(8)(9). At longer postinjection intervals (116-120 h), RGCs in the retina contralateral to the injection were also labeled by retrograde transport from infected retinorecipient neurons receiving a bilateral retinal input (Fig.…”

A Novel Human Opsin in the Inner Retina

“…In mice, only a small subset of widely distributed retinal ganglion and amacrine-like cells project to the SCN (Balkema and Dräger, 1990;Provencio et al, 1998a). The number and location of these cells are similar to that of the melanopsin-positive cells.…”

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

“…5). In the rat eye model, the wild-type virus PRV-Becker infects the projection neurons of the retina, the retinal ganglion cells, and spreads by anterograde transport in axons through the optic nerve to infect second order neurons in the suprachiasmatic nucleus, the dorsal lateral geniculate nucleus, the ventral lateral geniculate nucleus, the intergeniculate leaflet, and superior colliculus (66,287,327). PRV can be detected in secondorder neurons around 50 h postinoculation (64,323), consistent with a direct path to these retinorecipient structures.…”