Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

Trauma during critical periods of development can induce long‐lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This...

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Published in:Journal of neuroscience research Vol. 99; no. 1; pp. 90 - 109
Main Authors: Emmons, Randi, Sadok, Tasneem, Rovero, Natalie G., Belnap, Malia A., Henderson, Hannah J. M., Quan, Alex J., Del Toro, Noël J., Halladay, Lindsay R.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-01-2021
Subjects:
Anxiety
Anxiety disorders
Behavior
BNST
Children
extended amygdala
maternal separation
Motivation
postnatal stress
Reinforcement
RRID:AB_2535812
RRID:Addgene_50475
RRID:Addgene_50476
Separation
Social behavior
Social factors
social interaction
Social interactions
Stria terminalis
Trauma
Weaning
maternal separation
BNST
RRID:Addgene_50476
social interaction
extended amygdala
postnatal stress
RRID:AB_2535812
RRID:Addgene_50475
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Summary:Trauma during critical periods of development can induce long‐lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety‐like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2–5 and 8 hr/day on PD6‐16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two‐part social interaction task designed to test social motivation (choice between a same‐sex novel conspecific or an empty cup) and social novelty preference (choice between the original‐novel conspecific vs. a new‐novel conspecific). We used chemogenetics to non‐selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non‐stressed versus ELS mice; social motivation was decreased in non‐stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation—for which they were deficient prior—following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma. Early life stress (ELS) induces long‐lasting social behavior deficits. We used chemogenetics to manipulate activity in the bed nucleus of the stria terminalis (BNST), which undergoes maturation during the early postnatal period. Altering BNST activity in adulthood produced divergent effects on social behavior that were dependent upon history of ELS.
Bibliography:https://publons.com/publon/10.1002/jnr.24644
Randi Emmons and Tasneem Sadok contributed equally to this work.
Edited by Constanza Cortes. Reviewed by John Christianson and Brian Trainor.
The peer review history for this article is available at
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ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.24644