J Neurosci
Department of Psychology, Rutgers University, Piscataway, New Jersey 08854,
Published: March 2020
The bed nucleus of the stria terminalis (BNST) is a forebrain region highly responsive to stress that expresses corticotropin-releasing hormone (CRH) and is implicated in mood disorders, such as anxiety. However, the exact mechanism by which chronic stress induces CRH-mediated dysfunction in BNST and maladaptive behaviors remains unclear. Here, we first confirmed that selective acute optogenetic activation of the oval nucleus BNST (ovBNST) increases maladaptive avoidance behaviors in male mice. Next, we found that a 6 week chronic variable mild stress (CVMS) paradigm resulted in maladaptive behaviors and increased cellular excitability of ovBNST CRH neurons by potentiating mEPSC amplitude, altering the resting membrane potential, and diminishing M-currents (a voltage-gated K current that stabilizes membrane potential) in slices. CVMS also increased c-fos cells in ovBNST following handling. We next investigated potential molecular mechanism underlying the electrophysiological effects and observed that CVMS increased CRH and pituitary adenylate cyclase-activating polypeptide (PACAP; a CRH upstream regulator) cells but decreased striatal-enriched protein tyrosine phosphatase (a STEP CRH inhibitor) cells in ovBNST. Interestingly, the electrophysiological effects of CVMS were reversed by CRHR1-selective antagonist R121919 application. CVMS also activated protein kinase A (PKA) in BNST, and chronic infusion of the PKA-selective antagonist H89 into ovBNST reversed the effects of CVMS. Coadministration of the PKA agonist forskolin prevented the beneficial effects of R121919. Finally, CVMS induced an increase in surface expression of phosphorylated GluR1 (S845) in BNST. Collectively, these findings highlight a novel and indispensable stress-induced role for PKA-dependent CRHR1 signaling in activating BNST CRH neurons and mediating maladaptive behaviors. Chronic stress and acute activation of oval bed nucleus of the stria terminalis (ovBNST) induces maladaptive behaviors in rodents. However, the precise molecular and electrophysiological mechanisms underlying these effects remain unclear. Here, we demonstrate that chronic variable mild stress activates corticotropin-releasing hormone (CRH)-associated stress signaling and CRH neurons in ovBNST by potentiating mEPSC amplitude and decreasing M-current in male mice. These electrophysiological alterations and maladaptive behaviors were mediated by BNST protein kinase A-dependent CRHR1 signaling. Our results thus highlight the importance of BNST CRH dysfunction in chronic stress-induced disorders.
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http://dx.doi.org/10.1523/JNEUROSCI.2410-19.2020 | DOI Listing |
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Indonesian adolescents face an increased risk of developing mental health conditions such as depression and anxiety, largely due to insufficient mental health literacy and awareness. This lack of knowledge often leads to delayed recognition and treatment. To address this, the present descriptive qualitative study explores Indonesian adolescents' perceptions of mental health challenges and needs.
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View Article and Find Full Text PDFFront Psychol
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