Ex Vivo Modulation of the BNST by Parabrachial CGRP Projections Is Decreased After a History of Stress‐Induced Anxiety
Year: 2025
Type: article
Abstract: ABSTRACT Activity in the parabrachial calcitonin gene‐related peptide to bed nucleus of the stria terminalis (PBN[CGRP] → BNST) circuit associates with anxiety‐like behavior. To test whether previous stress‐induced anxiety is associated with neuronal adaptations in the PBN (CGRP) → BNST circuit, C57 mice were exposed to 4 days of daily forced swim stress (FSS). The novelty‐suppressed feeding test (NSFT) demonstrated repeated FSS increased anxiety‐like behavior. To assess if repeated FSS potentiates anxiety‐like behavior in mice with dysregulated affect, mice received chronic intermittent ethanol vapor followed by FSS in abstinence. Anxiety‐like behavior measured by NSFT was potentiated by repeated FSS in alcohol‐abstinence. To measure neuroadaptations associated with a history of stress, Calca CRE mice, with the Cre‐dependent hM3D(Gq) DREADDs, in the PBN and the GFP‐based Ca2+ sensor GCaMP7f in the bed nucleus of the stria terminalis (BNST), were exposed to repeated FSS and anxiety‐like behavior measured with the NSFT. Weeks later, neurotransmission was measured by recording GCaMP7f fluorescence in ex vivo BNST slices. hM3D(Gq) DREADDs in PBN (CGRP) projections were activated via bath application of clozapine‐n‐oxide. PBN (CGRP) projections increased GCaMP7f spike frequency in the BNST in naïve conditions but not after a history of repeated FSS. Post‐activation of PBN (CGRP) projections decreased GCaMP frequency and amplitude in the BNST, which was potentiated by a history of repeated FSS. These findings extend the anxiogenic role of PBN (CGRP) neurons by demonstrating neurotransmission in the PBN (CGRP) → BNST circuit is dysregulated after a stress‐induced anxiogenic state. Given the potential of CGRP‐related therapies, future studies will investigate the role of CGRP within the PBN → BNST circuit in inducing anxiety‐related neuroadaptations.
Source: European Journal of Neuroscience
DOI: 10.1111/ejn.70268
Authors: L. S. Kayat, N. Petersen, C. E. Van Doorn, B. P. Nabit, J. B. Tyree, S. W. Centanni, A. A. Jaramillo
Institutions: Vanderbilt University, University of Kentucky
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,560
Awards: G2317489585, G3326603717, Medical Scientist Training Program, G4142829256, Insular Cortex-BNST neural circuit regulation of chronic alcohol abstinence-induced negative affect, Neuron-astrocyte interactions mediating ethanol and noradrenergic modulation of wake-promoting vPAG dopamine neurons, Extended amygdala mGlu8 receptor signaling in stress-reward interactions, Neuropeptide-dependent parabrachial control of the BNST during alcohol abstinence-induced negative affect, Insular cortex-BNST neural circuit regulation of chronic alcohol abstinence-induced negative affect, Norepinephrine-dopamine interactions underlying arousal, Neuropeptide-dependent parabrachial control of the BNST during alcohol abstinence-induced negative affect, COBRE for Translational Chemical Biology, Research Training in Drug Abuse Behavior
OpenAlex ID: W4416202563