Modulation of the BNST by Parabrachial CGRP projections is enhanced in a
state of stress-induced anxiety and hyperphagia
Abstract
Activity in the parabrachial calcitonin gene-related peptide to bed
nucleus of the stria terminalis circuit associates with anxiety-like
behavior. To test whether heightened anxiety induces neuronal
adaptations in parabrachial to bed nucleus of the stria terminalis
circuit, C57 mice were exposed to 4 days of daily forced swim stress.
The novelty suppressed feeding test demonstrated the forced swim stress
model increased anxiety-like behavior and induced hyperphagia. To assess
if forced swim stress potentiates anxiety-like behavior in mice with
baseline dysregulated affect, mice received chronic intermittent ethanol
vapor and forced swim stress in alcohol-abstinence. Anxiety-like
behavior measured by the novelty suppressed feeding test was potentiated
and hyperphagia was induced by forced swim stress in alcohol-abstinence.
To measure anxiety-related neuroadaptations, CalcaCRE mice, with of
CRE-dependent hM3D(Gq) DREADDs in the parabrachial nucleus and the Ca2+
sensor GCaMP7f in the bed nucleus of the stria terminalis, were exposed
to forced swim stress. Neurotransmission was measured by recording
GCaMP7f fluorescence in ex vivo bed nucleus of the stria terminalis
slices. hM3D(Gq) DREADDs in parabrachial projections expressing
calcitonin gene-related peptide were activated via bath application of
clozapine-n-oxide. Excitatory drive by parabrachial calcitonin
gene-related peptide projections decreased GCaMP7f spike frequency and
amplitude in the bed nucleus of the stria terminalis. Forced swim stress
potentiated excitatory drive of parabrachial calcitonin gene-related
peptide projections as the decrease in GCaMP frequency was potentiated.
In summary repeated exposure to stress induces heightened anxiety and
hyperphagia that is associated with potentiated parabrachial to bed
nucleus of the stria terminalis circuit activity.