Abstract
Abstract INTRODUCTION Inhibitory interneuron transplantation is a prospective treatment for neuropsychiatric disorders, but it is unclear whether transplantation might elicit therapeutic effects by reversing preexisting abnormalities, nonspecifically increasing synaptic inhibition, or engaging mechanisms that vary depending on recipient background and behavioral state. METHODS We transplanted wild-type embryonic interneuron precursors into mice lacking an autism-associated gene, Pten, in inhibitory interneurons. Additionally, we performed transplantation into wild-type recipient mice, and then examined the recipient behavior, cellular physiology in Vitro, and network physiology in Vivo. RESULTS Transplantation rescued social behavior deficits in Pten mutants without normalizing excessive synaptic inhibition in Vitro or reduced baseline gamma oscillatory power in Vivo. However, transplantation altered recipient electroencephalography (EEG) responses observed specifically during periods of social interaction. When transplantation was performed into wild-type recipients, the subtype composition of the transplanted population varied from that observed in Pten mutants, and, moreover, recipients did not exhibit alterations to social behavior or related EEG responses. CONCLUSION Interneuron transplantation elicits recipient- and behavioral state-dependent effects, and normalizes behavior by creating new patterns of network activity, rather than restoring wild-type states. Interneuron transplantation may provide a novel therapeutic approach to the treatment of autism and related neuropsychiatric disorders.
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