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Author Notes:

E-mail: shannon.l.gourley@emory.edu

We thank A. Allen and Lauren Shapiro for valuable contributions and Dr. Mary Torregrossa for critical comments on the manuscript.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

NIH https://www.nih.gov/ (grant number MH101477). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

NIH https://www.nih.gov/ (grant number T32 GM008602).

NIH https://www.nih.gov/ (grant number P30NS055077).

NIH https://www.nih.gov/ (grant number OD P51OD011132).

NSF https://www.nsf.gov/ (grant number DGE-1444932).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biology
  • Life Sciences & Biomedicine - Other Topics
  • INSTRUMENTAL CONTINGENCY DEGRADATION
  • MEDIAL PREFRONTAL CORTEX
  • NEUROTROPHIC FACTOR
  • CULTURED HIPPOCAMPAL
  • ENTORHINAL CORTEX
  • RECEPTOR ISOFORMS
  • ANIMAL-MODEL
  • BRAIN
  • NEURONS
  • AMYGDALA

Journal Title:

PLoS Biology

Volume:

Volume 15, Number 11

Publisher:

, Pages e2003000-e2003000

Type of Work:

Article | Final Publisher PDF

Abstract:

In humans and rodents, stress promotes habit-based behaviors that can interfere with action—outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent—primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB—ERK42/44 tone determines long-term behavioral outcomes.

Copyright information:

© 2017 Barfield et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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