ArticleBiological psychiatry global open science2023
PACAP Controls Endocrine and Behavioral Stress Responses via Separate Brain Circuits.
Article in Biological psychiatry global open science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Lateral septal PACAP signaling regulates stress and anxiety reactions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Top-down medial prefrontal cortex-to-hypothalamic paraventricular nucleus circuit regulates social avoidance and conditioned fear in male mice.Cell discovery · 2026Article
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Review
- Article
- A chemogenetic approach for temporal and cell-specific activation of endogenous GPCRs in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neural Regulation of Blood Glucose in Acute Stress: A Report on Research Supported by Pathway to Stop Diabetes.Diabetes · 2026Review
- Selective vulnerability of GABAergic neurons in chronic migraine.The journal of headache and pain · 2025Article
- Pituitary adenylate cyclase-activating polypeptide modulates circadian feeding and emotional behavior in mice independent of stress-induced hyperphagia.Veterinary world · 2025Article
- PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.Frontiers in neuroscience · 2025Review
- Association between social dominance hierarchy and PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice.Scientific reports · 2024Article
- Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.Frontiers in psychiatry · 2024Review
- Article
- Impact of social dominance hierarchy on PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Background: The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a master regulator of central and peripheral stress responses, yet it is not clear how PACAP projections throughout the brain execute endocrine and behavioral stress responses. Methods: We used AAV (adeno-associated virus) neuronal tracing, an acute restraint stress (ARS) paradigm, and intersectional genetics, in C57BL/6 mice, to identify PACAP-containing circuits controlling stress-induced behavior and endocrine activation. Results: PACAP deletion from forebrain excitatory neurons, including a projection directly from medial prefrontal cortex to hypothalamus, impairs c-fos activation and corticotropin-releasing hormone (CRH) messenger RNA elevation in the paraventricular nucleus after 2 hours of restraint, without affecting ARS-induced hypophagia, or c-fos elevation in nonhypothalamic brain. Elimination of PACAP within projections from lateral parabrachial nucleus to extended amygdala, on the other hand, attenuates ARS-induced hypophagia, along with extended amygdala fos induction, without affecting ARS-induced CRH messenger RNA elevation in the paraventricular nucleus. PACAP projections to extended amygdala terminate at protein kinase C delta type (PKCδ) neurons in both the central amygdala and the oval bed nucleus of the stria terminalis. Silencing of PKCδ neurons in the central amygdala, but not in the oval bed nucleus of the stria terminalis, attenuates ARS-induced hypophagia. Experiments were carried out in mice of both sexes with Conclusions: A frontocortical descending PACAP projection controls paraventricular nucleus CRH messenger RNA production to maintain hypothalamic-pituitary-adrenal axis activation and regulate the endocrine response to stress. An ascending PACAPergic projection from the external lateral parabrachial nucleus to PKCδ neurons in the central amygdala regulates behavioral responses to stress. Defining two separate limbs of the acute stress response provides broader insight into the specific brain circuitry engaged by the psychogenic stress response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.