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Combining mGRASP and optogenetics enables high-resolution functional mapping of descending cortical projections

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Title: Combining mGRASP and optogenetics enables high-resolution functional mapping of descending cortical projections
Authors: Song, JH
Lucaci, D
Calangiu, I
Brown, MTC
Park, JS
Kim, J
Brickley, SG
Chadderton, PT
Item Type: Journal Article
Abstract: We have applied optogenetics and mGRASP, a light microscopy technique that labels synaptic contacts, to map the number and strength of defined corticocollicular (CC) connections. Using mGRASP, we show that CC projections form small, medium, and large synapses, and both the number and the distribution of synapse size vary among the IC regions. Using optogenetics, we show that low-frequency stimulation of CC axons expressing channelrhodopsin produces prolonged elevations of the CC miniature EPSC (mEPSC) rate. Functional analysis of CC mEPSCs reveals small-, medium-, and large-amplitude events that mirror the synaptic distributions observed with mGRASP. Our results reveal that descending ipsilateral projections dominate CC feedback via an increased number of large synaptic contacts, especially onto the soma of IC neurons. This study highlights the feasibility of combining microscopy (i.e., mGRASP) and optogenetics to reveal synaptic weighting of defined projections at the level of single neurons, enabling functional connectomic mapping in diverse neural circuits.
Issue Date: 24-Jul-2018
Date of Acceptance: 18-Jun-2018
URI: http://hdl.handle.net/10044/1/61582
DOI: https://dx.doi.org/10.1016/j.celrep.2018.06.076
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 1071
End Page: 1080
Journal / Book Title: Cell Reports
Volume: 24
Issue: 4
Copyright Statement: © 2018 The Author(s). This is an open access article under the CC-BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Medical Research Council (MRC)
Commission of the European Communities
Human Frontier Science Program
Medical Research Foundation
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: G1000512
PIEF-GA-2012-331858
RGY089/2012
C0488
BB/N008871/1
Keywords: corticofugal
functional connectomics
synapse
synaptic integration
Publication Status: Published
Online Publication Date: 2018-07-24
Appears in Collections:Faculty of Engineering
Bioengineering
Faculty of Natural Sciences



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