Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring

Science  07 Feb 2014:
Vol. 343, Issue 6171, pp. 675-679
DOI: 10.1126/science.1247190

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The Switch That Doesn't

In mammals, a class of neurons in the brain normally switches from excitatory to inhibitory functions at birth. Tyzio et al. (p. 675; see the Perspective by Zimmerman and Connors) studied how these neurons function in rat and mouse models of autism. The results show that oxytocin normally accelerates the switch in function, but in these two animal models, the switch fails. The dysfunction could be replicated in normal animals using an oxytocin receptor antagonist.


We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naïve mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.

  • * These authors contributed equally to this work.

  • On leave from Tehran University of Medical Sciences, Tehran, Iran.

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