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

Keun-Young Kim; Luis C Rios; Hiep Le; Alex J Perez; Sébastien Phan; Eric A Bushong; Thomas J Deerinck; Yu Hsin Liu; Maya A Ellisman; Varda Lev-Ram; Suyeon Ju; Sneha A Panda; Sanghee Yoon; Masatoshi Hirayama; Ludovic S Mure; Megumi Hatori; Mark H Ellisman; Satchidananda Panda

doi:10.1016/j.celrep.2019.09.006

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

Cell Rep. 2019 Oct 15;29(3):628-644.e6. doi: 10.1016/j.celrep.2019.09.006.

Authors

Keun-Young Kim¹, Luis C Rios², Hiep Le², Alex J Perez³, Sébastien Phan¹, Eric A Bushong¹, Thomas J Deerinck¹, Yu Hsin Liu⁴, Maya A Ellisman⁵, Varda Lev-Ram⁶, Suyeon Ju³, Sneha A Panda³, Sanghee Yoon³, Masatoshi Hirayama², Ludovic S Mure², Megumi Hatori², Mark H Ellisman⁷, Satchidananda Panda⁸

Affiliations

¹ Department of Neurosciences, University of California at San Diego School of Medicine, La Jolla, CA, USA; National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
² Salk Institute for Biological Studies, La Jolla, CA, USA.
³ National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
⁴ Salk Institute for Biological Studies, La Jolla, CA, USA; Medical Scientist Training Program, University of California at San Diego School of Medicine, La Jolla, CA, USA.
⁵ Biological Sciences Graduate Training Program, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
⁷ Department of Neurosciences, University of California at San Diego School of Medicine, La Jolla, CA, USA; National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA. Electronic address: mellisman@ucsd.edu.
⁸ Salk Institute for Biological Studies, La Jolla, CA, USA. Electronic address: satchin@salk.edu.

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.

Keywords: IGL; LGN; OPN; SCN; circadian; ipRGC; mRGC; melanopsin; miniSOG; serial blockface electron microscopy.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Axons / physiology
Brain / metabolism*
Brain / pathology
Circadian Rhythm / physiology
Female
Male
Mice
Mice, Knockout
Microscopy, Electron
Pretectal Region / metabolism
Pretectal Region / pathology
Retinal Ganglion Cells / metabolism*
Retinal Ganglion Cells / pathology
Rod Opsins / deficiency
Rod Opsins / genetics
Rod Opsins / metabolism*
Suprachiasmatic Nucleus / metabolism
Suprachiasmatic Nucleus / pathology
Synapses / metabolism*

Substances

Rod Opsins
melanopsin

Abstract

Publication types

MeSH terms

Substances

Grants and funding