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

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 sen...

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Bibliographic Details
Published in:The Journal of neuroscience 2014-09, Vol.34 (37), p.12379-12393
Main Authors: Rebello, Tahilia J, Yu, Qinghui, Goodfellow, Nathalie M, Caffrey Cagliostro, Martha K, Teissier, Anne, Morelli, Emanuela, Demireva, Elena Y, Chemiakine, Alexei, Rosoklija, Gorazd B, Dwork, Andrew J, Lambe, Evelyn K, Gingrich, Jay A, Ansorge, Mark S
Format: Article
Language:English
Subjects:
Aging - metabolism
Animals
Animals, Newborn
Anxiety - complications
Anxiety - metabolism
Behavior, Animal
Depression - complications
Depression - metabolism
Extinction, Psychological
Fear
Female
Life Sciences
Male
Mice
Neurons and Cognition
Prefrontal Cortex - physiopathology
Serotonin - metabolism
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.1020-13.2014