Abstract
The form and synaptic fine structure of melanopsin-expressing retinal ganglion cells, also called intrinsically photosensitive retinal ganglion cells (ipRGCs), were determined using a new membrane-targeted version of a genetic probe for correlated light and electron microscopy (CLEM). ipRGCs project to multiple brain regions, and because the method labels the entire neuron, it was possible to analyze nerve terminals in multiple retinorecipient brain regions, including the suprachiasmatic nucleus (SCN), olivary pretectal nucleus (OPN), and subregions of the lateral geniculate. Although ipRGCs provide the only direct retinal input to the OPN and SCN, ipRGC terminal arbors and boutons were found to be remarkably different in each target region. A network of dendro-dendritic chemical synapses (DDCSs) was also revealed in the SCN, with ipRGC axon terminals preferentially synapsing on the DDCS-linked cells. The methods developed to enable this analysis should propel other CLEM studies of long-distance brain circuits at high resolution.
Highlights
Photosensitive retinal ganglion cells express the photopigment melanopsin (Opn4) and are essential for non-image-forming visual processes (Hatori et al, 2008; Hattar et al, 2002)
IpRGCs provide the only direct retinal input to the olivary pretectal nucleus (OPN) and suprachiasmatic nucleus (SCN), Intrinsically photosensitive retinal ganglion cells (ipRGCs) terminal arbors and boutons were found to be remarkably different in each target region
A network of dendro-dendritic chemical synapses (DDCSs) was revealed in the SCN, with ipRGC axon terminals preferentially synapsing on the DDCS-linked cells
Summary
Photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin (Opn4) and are essential for non-image-forming visual processes (Hatori et al, 2008; Hattar et al, 2002). IpRGC axons send collaterals to several subregions of the lateral geniculate nucleus (LGN). Light information travels ~10 mm through ipRGC axons to the suprachiasmatic nucleus (SCN) to facilitate circadian photoentrainment and ~15 mm to reach the olivary pretectal nucleus (OPN) to mediate pupillary constriction in response to light ( known as the pupillary light reflex [PLR]) (Hatori and Panda, 2010; Figure 1A). This diverse pattern of central projections parallels the diversity in photoresponse properties exhibited by these brain regions (e.g., different threshold sensitivities and kinetics). How the ipRGC facilitates such temporally and spatially diverse functions remains unknown
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