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
Affiliations
Keun-Young Kim
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
Luis C. Rios
Salk Institute for Biological Studies, La Jolla, CA, USA
Hiep Le
Salk Institute for Biological Studies, La Jolla, CA, USA
Alex J. Perez
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA
Sébastien Phan
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
Eric A. Bushong
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
Thomas J. Deerinck
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
Yu Hsin Liu
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
Maya A. Ellisman
Biological Sciences Graduate Training Program, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
Varda Lev-Ram
Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA
Suyeon Ju
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA
Sneha A. Panda
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA
Sanghee Yoon
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA
Masatoshi Hirayama
Salk Institute for Biological Studies, La Jolla, CA, USA
Ludovic S. Mure
Salk Institute for Biological Studies, La Jolla, CA, USA
Megumi Hatori
Salk Institute for Biological Studies, La Jolla, CA, USA
Mark H. Ellisman
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; Corresponding author
Satchidananda Panda
Salk Institute for Biological Studies, La Jolla, CA, USA; Corresponding author
Summary: 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. : 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. Keywords: melanopsin, mRGC, ipRGC, circadian, SCN, OPN, miniSOG, serial blockface electron microscopy, LGN, IGL
