Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency.

Journal Article (Journal Article)

Although the majority of first-line antidepressants increase brain serotonin and rare polymorphisms in tryptophan hydroxlase-2 (Tph2), the rate-limiting enzyme in the brain serotonin synthesis pathway, have been identified in cohorts of subjects with major depressive disorder, the circuit level alterations that results from serotonergic hypofunction remain poorly understood. Here we use chronic multicircuit neurophysiological recordings to characterize functional interactions across cortical and limbic circuits in mice engineered to express a human loss-of-function depression allele Tph2-(R441H) [Tph2 knockin (Tph2KI)]. Our results show that Tph2KI mice exhibit increased intra-network synchrony within medial prefrontal cortex (mPFC) and basal amygdala (AMY) and increased inter-network synchrony between these two brain networks. Moreover, we demonstrate that chronic treatment with fluoxetine reverses several of the circuit alterations observed within Tph2KI mice. Together, our findings establish a functional link between functional hyposerotonergia and altered mPFC-AMY network dynamics.

Full Text

Duke Authors

Cited Authors

  • Dzirasa, K; Kumar, S; Sachs, BD; Caron, MG; Nicolelis, MAL

Published Date

  • March 6, 2013

Published In

Volume / Issue

  • 33 / 10

Start / End Page

  • 4505 - 4513

PubMed ID

  • 23467366

Pubmed Central ID

  • PMC3633471

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.4891-12.2013


  • eng

Conference Location

  • United States