Publications
1. Choe, Katrina Y; Bethlehem, Richard A I; Safrin, Martin; Dong, Hongmei; Salman, Elena; Li, Ying; Grinevich, Valery; Golshani, Peyman; DeNardo, Laura A; Peñagarikano, Olga; Harris, Neil G; Geschwind, Daniel H
Oxytocin normalizes altered circuit connectivity for social
rescue of the Cntnap2 knockout mouse Journal Article
In: Neuron, vol. 110, no. 5, pp. 795–808.e6, 2022.
Abstract | BibTeX | Tags: autism; brain network; fMRI; functional connectivity; iDISCO; mouse model; nucleus accumbens; oxytocin; paraventricular nucleus; social behavior
@article{Choe2022-ld,
title = {Oxytocin normalizes altered circuit connectivity for social
rescue of the Cntnap2 knockout mouse},
author = {Katrina Y Choe and Richard A I Bethlehem and Martin Safrin and Hongmei Dong and Elena Salman and Ying Li and Valery Grinevich and Peyman Golshani and Laura A DeNardo and Olga Peñagarikano and Neil G Harris and Daniel H Geschwind},
year = {2022},
date = {2022-03-01},
journal = {Neuron},
volume = {110},
number = {5},
pages = {795–808.e6},
publisher = {Elsevier BV},
abstract = {The neural basis of abnormal social behavior in autism spectrum
disorders (ASDs) remains incompletely understood. Here we used
two complementary but independent brain-wide mapping approaches,
mouse resting-state fMRI and c-Fos-iDISCO+ imaging, to construct
brain-wide activity and connectivity maps of the Cntnap2
knockout (KO) mouse model of ASD. At the macroscale level, we
detected reduced functional coupling across social brain regions
despite general patterns of hyperconnectivity across major brain
structures. Oxytocin administration, which rescues social
deficits in KO mice, strongly stimulated many brain areas and
normalized connectivity patterns. Notably, chemogenetically
triggered release of endogenous oxytocin strongly stimulated the
nucleus accumbens (NAc), a forebrain nucleus implicated in
social reward. Furthermore, NAc-targeted approaches to activate
local oxytocin receptors sufficiently rescued their social
deficits. Our findings establish circuit- and systems-level
mechanisms of social deficits in Cntnap2 KO mice and reveal the
NAc as a region that can be modulated by oxytocin to promote
social interactions.},
keywords = {autism; brain network; fMRI; functional connectivity; iDISCO; mouse model; nucleus accumbens; oxytocin; paraventricular nucleus; social behavior},
pubstate = {published},
tppubtype = {article}
}
The neural basis of abnormal social behavior in autism spectrum
disorders (ASDs) remains incompletely understood. Here we used
two complementary but independent brain-wide mapping approaches,
mouse resting-state fMRI and c-Fos-iDISCO+ imaging, to construct
brain-wide activity and connectivity maps of the Cntnap2
knockout (KO) mouse model of ASD. At the macroscale level, we
detected reduced functional coupling across social brain regions
despite general patterns of hyperconnectivity across major brain
structures. Oxytocin administration, which rescues social
deficits in KO mice, strongly stimulated many brain areas and
normalized connectivity patterns. Notably, chemogenetically
triggered release of endogenous oxytocin strongly stimulated the
nucleus accumbens (NAc), a forebrain nucleus implicated in
social reward. Furthermore, NAc-targeted approaches to activate
local oxytocin receptors sufficiently rescued their social
deficits. Our findings establish circuit- and systems-level
mechanisms of social deficits in Cntnap2 KO mice and reveal the
NAc as a region that can be modulated by oxytocin to promote
social interactions.