Activation of the hypothalamic-pituitary-adrenal (HPA) axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. The mechanisms and neural circuits that drive emotion and cognition are inextricably linked.

Laboratory of Neuroanatomy and Behavior, Department of Psychology, Northeastern University, Boston, MA, USA.

This will aid in the development of novel therapeutic targets for stress-induced cognitive dysfunction.Ĭorticotropin-releasing factor receptor 1 Executive dysfunction Prefrontal cortex Reversal learning Stress Temporal order memory.Ĭopyright © 2016 Society of Biological Psychiatry. Taken together, these results unravel a molecular mechanism linking acute stress to executive dysfunction via CRFR1. Finally, PKA blockade reverses the intra-mPFC CRF-induced executive dysfunction.

Acute stress and intra-mPFC CRF activate the PKA signaling pathway in the mPFC, leading to cyclic AMP response element binding protein phosphorylation in intra-mPFC CRFR1-expressing neurons. Importantly, intra-mPFC CRFR1 deletion abolishes acute stress-induced executive dysfunction, whereas intra-mPFC CRF mimics acute stress-induced mPFC dysfunction.

We report acute stress-induced effects on mPFC-mediated cognition, identify CRF-CRFR1-containing microcircuits within the mPFC, and demonstrate stress-induced changes in Crhr1 messenger RNA expression. Finally, mice received intra-mPFC CRF (n = 11) and/or Rp-isomer cyclic adenosine 3',5' monophosphorothioate (Rp-cAMPS) (n = 12) microinjections and underwent behavioral testing. Co-immunoprecipitation was used to detect activation of the protein kinase A (PKA) signaling pathway in the mPFC of acutely stressed mice (n = 8) or intra-mPFC CRF injected mice (n = 7). Crhr1 loxP/loxP mice received either intra-mPFC adeno-associated virus-Cre or empty microinjections (n = 17-20) and then were submitted to acute stress and later to the behavioral tests. Changes in mPFC Crhr1 messenger RNA levels were measured in acutely stressed mice (n = 12). Mice were exposed to acute social defeat stress and subsequently to either the temporal order memory (n = 11-12) or reversal learning (n = 9-11) behavioral test. However, its contribution to the effects of stress in the mPFC remains unclear. Corticotropin-releasing factor (CRF), through CRF receptor 1 (CRFR1), constitutes a key element of the stress response. The medial prefrontal cortex (mPFC) subserves complex cognition and is impaired by stress.

Stress induced hedonic dysfunction