Synaptic Specializations of Melanopsin-Retinal Ganglion Cells in Multiple Brain Regions Revealed by Genetic Label for Light and Electron Microscopy

• Published in: Cell reports (Cambridge) Vol. 29; no. 3; pp. 628 - 644.e6
• Main Authors: Kim, Keun-Young, Rios, Luis C., Le, Hiep, Perez, Alex J., Phan, Sébastien, Bushong, Eric A., Deerinck, Thomas J., Liu, Yu Hsin, Ellisman, Maya A., Lev-Ram, Varda, Ju, Suyeon, Panda, Sneha A., Yoon, Sanghee, Hirayama, Masatoshi, Mure, Ludovic S., Hatori, Megumi, Ellisman, Mark H., Panda, Satchidananda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2019; Elsevier
• Subjects: Animals; Axons - physiology; Brain - metabolism; Brain - pathology; circadian; Circadian Rhythm - physiology; Female; IGL; ipRGC; LGN; Male; melanopsin; Mice; Mice, Knockout; Microscopy, Electron; miniSOG; mRGC; OPN; Pretectal Region - metabolism; Pretectal Region - pathology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Rod Opsins - deficiency; Rod Opsins - genetics; Rod Opsins - metabolism; SCN; serial blockface electron microscopy; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - pathology; Synapses - metabolism; melanopsin; circadian; LGN; mRGC; serial blockface electron microscopy; miniSOG; ipRGC; OPN; SCN; IGL
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.09.006

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. [Display omitted] •Membrane-tethered miniSOG for correlated light and electron microscopy in vivo•Melanopsin RGCs show brain region-specific arborization and synaptic structures•A subset of SCN neurons network through dendrodendritic chemical synapses (DDCS)•SCN neurons in DDCS network receive a higher melanopsin RGC input Kim et al. express a genetically encoded electron microscopy (EM) tag in mRGCs of the mouse retina and use serial block-face electron microscopy to analyze the optic nerve and synaptic neuropil in five different brain regions. They find that mRGC synaptic terminals show target-specific specializations corresponding to differences in responses to light.