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

Publication ,  Journal Article
Dzirasa, K; Kumar, S; Sachs, BD; Caron, MG; Nicolelis, MAL
Published in: J Neurosci
March 6, 2013

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.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

March 6, 2013

Volume

33

Issue

10

Start / End Page

4505 / 4513

Location

United States

Related Subject Headings

  • Tryptophan Hydroxylase
  • Spectrum Analysis
  • Serotonin
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
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ICMJE
MLA
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Dzirasa, K., Kumar, S., Sachs, B. D., Caron, M. G., & Nicolelis, M. A. L. (2013). Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency. J Neurosci, 33(10), 4505–4513. https://doi.org/10.1523/JNEUROSCI.4891-12.2013
Dzirasa, Kafui, Sunil Kumar, Benjamin D. Sachs, Marc G. Caron, and Miguel A. L. Nicolelis. “Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency.J Neurosci 33, no. 10 (March 6, 2013): 4505–13. https://doi.org/10.1523/JNEUROSCI.4891-12.2013.
Dzirasa K, Kumar S, Sachs BD, Caron MG, Nicolelis MAL. Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency. J Neurosci. 2013 Mar 6;33(10):4505–13.
Dzirasa, Kafui, et al. “Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency.J Neurosci, vol. 33, no. 10, Mar. 2013, pp. 4505–13. Pubmed, doi:10.1523/JNEUROSCI.4891-12.2013.
Dzirasa K, Kumar S, Sachs BD, Caron MG, Nicolelis MAL. Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency. J Neurosci. 2013 Mar 6;33(10):4505–4513.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

March 6, 2013

Volume

33

Issue

10

Start / End Page

4505 / 4513

Location

United States

Related Subject Headings

  • Tryptophan Hydroxylase
  • Spectrum Analysis
  • Serotonin
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice