Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development

TitleCircuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development
Publication TypeJournal Article
Year of Publication2017
AuthorsBath KG, Russo SJ, Pleil KE, Wohleb ES, Duman RS, Radley JJ
JournalNeurobiol Stress
Volume7
Pagination137-151
Date Published2017 Dec
ISSN2352-2895
Abstract

The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

DOI10.1016/j.ynstr.2017.05.001
Alternate JournalNeurobiol Stress
PubMed ID29276735
PubMed Central IDPMC5736942
Grant ListR01 MH095972 / MH / NIMH NIH HHS / United States
R01 MH104559 / MH / NIMH NIH HHS / United States
P20 GM103430 / GM / NIGMS NIH HHS / United States
R37 MH045481 / MH / NIMH NIH HHS / United States
K99 AA023559 / AA / NIAAA NIH HHS / United States
R01 MH090264 / MH / NIMH NIH HHS / United States
P50 AT008661 / AT / NCCIH NIH HHS / United States
R56 MH095972 / MH / NIMH NIH HHS / United States
F32 AA021043 / AA / NIAAA NIH HHS / United States
R01 MH119106 / MH / NIMH NIH HHS / United States
R01 MH093897 / MH / NIMH NIH HHS / United States
R01 MH105910 / MH / NIMH NIH HHS / United States
R00 AA023559 / AA / NIAAA NIH HHS / United States