RT Journal Article
SR Electronic
T1 Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12379
OP 12393
DO 10.1523/JNEUROSCI.1020-13.2014
VO 34
IS 37
A1 Tahilia J. Rebello
A1 Qinghui Yu
A1 Nathalie M. Goodfellow
A1 Martha K. Caffrey Cagliostro
A1 Anne Teissier
A1 Emanuela Morelli
A1 Elena Y. Demireva
A1 Alexei Chemiakine
A1 Gorazd B. Rosoklija
A1 Andrew J. Dwork
A1 Evelyn K. Lambe
A1 Jay A. Gingrich
A1 Mark S. Ansorge
YR 2014
UL http://www.jneurosci.org/content/34/37/12379.abstract
AB 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 5-HT transporter (5-HTT) blockade increasing anxiety- and depression-like behavior, and impairing fear extinction learning and memory in adult mice. Concomitantly, P2–P11 5-HTT blockade causes dendritic hypotrophy and reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote fear extinction. By contrast, the neighboring prelimbic (PL) pyramidal neurons, which normally inhibit fear extinction, become more excitable. Excitotoxic IL but not PL lesions in adult control mice reproduce the anxiety-related phenotypes. These findings suggest that increased 5-HT signaling during P2–P11 alters adult mPFC function to increase anxiety and impair fear extinction, and imply a differential role for IL and PL neurons in regulating affective behaviors. Together, our results support a developmental mechanism for the etiology and pathophysiology of affective disorders and fear-related behaviors.