Postnatal day 2 to 11 constitutes a 5-HT-sensitive period impacting adult mPFC function.

摘要: Early-life serotonin [5-hydroxytryptamine (5-HT)] signaling modulates brain development, which impacts adult behavior, but 5-HT-sensitive periods, neural substrates, and behavioral consequences remain poorly understood. Here we identify the period ranging from postnatal day 2 (P2) to P11 as 5-HT sensitive, with transporter (5-HTT) blockade increasing anxiety- depression-like impairing fear extinction learning memory in mice. Concomitantly, P2–P11 5-HTT causes dendritic hypotrophy reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote extinction. By contrast, neighboring prelimbic (PL) neurons, inhibit extinction, become more excitable. Excitotoxic IL not PL lesions control mice reproduce anxiety-related phenotypes. These findings suggest increased during alters mPFC function increase anxiety impair imply a differential role for regulating affective behaviors. Together, our results support developmental mechanism etiology pathophysiology disorders fear-related