TY - JOUR
T1 - Oxytocin as a Modulator of Synaptic Plasticity
T2 - Implications for Neurodevelopmental Disorders
AU - Rajamani, Keerthi Thirtamara
AU - Wagner, Shlomo
AU - Grinevich, Valery
AU - Harony-Nicolas, Hala
N1 - Publisher Copyright: © Copyright © 2018 Thirtamara Rajamani, Wagner, Grinevich and Harony-Nicolas.
PY - 2018/6/19
Y1 - 2018/6/19
N2 - The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits. Large-scale whole-exome sequencing studies in subjects with ASD, along with biochemical and electrophysiological studies in animal models of the disorder, indicate several risk genes that play an essential role in brain synapses, suggesting that deficits in synaptic activity and plasticity underlie the pathophysiology in a considerable portion of these cases. OXT has been repeatedly shown, both in vitro and in vivo, to modify synaptic properties and plasticity and to modulate neural activity in circuits that regulate social behavior. Together, these findings led us to hypothesize that failure of the OXT system during early development, as a direct or indirect consequence of genetic mutations, may impact social behavior by altering synaptic activity and plasticity. In this article, we review the evidence that support our hypothesis.
AB - The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits. Large-scale whole-exome sequencing studies in subjects with ASD, along with biochemical and electrophysiological studies in animal models of the disorder, indicate several risk genes that play an essential role in brain synapses, suggesting that deficits in synaptic activity and plasticity underlie the pathophysiology in a considerable portion of these cases. OXT has been repeatedly shown, both in vitro and in vivo, to modify synaptic properties and plasticity and to modulate neural activity in circuits that regulate social behavior. Together, these findings led us to hypothesize that failure of the OXT system during early development, as a direct or indirect consequence of genetic mutations, may impact social behavior by altering synaptic activity and plasticity. In this article, we review the evidence that support our hypothesis.
KW - animal models for ASD
KW - autism spectrum disorder (ASD)
KW - neurodevelopmental disorder
KW - oxytocin
KW - synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85066063597&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fnsyn.2018.00017
DO - https://doi.org/10.3389/fnsyn.2018.00017
M3 - Review article
C2 - 29970997
SN - 1663-3563
VL - 10
JO - Frontiers in Synaptic Neuroscience
JF - Frontiers in Synaptic Neuroscience
M1 - 17
ER -