Kölliker–Fuse/Parabrachial Complex PACAP—Glutamate Pathway to the Extended Amygdala Couples Rapid Autonomic and Delayed Endocrine Responses to Acute Hypotension
Year: 2025
Type: article
Abstract: The calyx of Held is a giant axo-somatic synapse classically confined to the auditory brainstem. We recently identified morphologically similar calyx-like terminals in the extended amygdala (EA) that arise from the ventrolateral parabrachial complex and co-express PACAP, CGRP, VAChT, VGluT1, and VGluT2, targeting PKCδ+/GluD1+ EA neurons. Here we asked whether this parabrachial–EA pathway participates in compensation during acute hypotension. In rats given hydralazine (10 mg/kg , i .p.), we quantified Fos protein during an early phase (60 min) and a late phase (120 min). Early after hypotension, Fos surged in a discrete subpopulation of the parabrachial Kölliker–Fuse (KF) region and in the EA, whereas magnocellular neurons of the supraoptic and paraventricular nuclei (SON/PVN) remained largely silent. By 120 min, magnocellular SON/PVN neurons were robustly Fos-positive. Confocal immunohistochemistry showed that most Fos+ PKCδ/GluD1 EA neurons were encircled by PACAP+ perisomatic terminals (80.8%), of which the majority co-expressed VGluT1 (88.1%). RNAscope in situ hybridization further identified a selective KF population co-expressing Adcyap1 (PACAP) and Slc17a7 (VGluT1) that became Fos-positive during the early phase. Together these data suggest that a KF PACAP/VGluT1 projection forms calyceal terminals around PKCδ/GluD1 EA neurons, providing a high-fidelity route for rapid autonomic rebound to falling blood pressure, while slower endocrine support is subsequently recruited via neurohormone-magnocellular activation. This work links multimodal parabrachial output to temporally layered autonomic-neuroendocrine control. Short abstract Acute hypotension triggers rapid autonomic compensation followed by slower endocrine support. We identify a Kölliker-Fuse (KF) PACAP/VGluT1 pathway to the extended amygdala (EA) that initiates the fast limb. In hydralazine-treated rats, Fos rose at 60 min in KF and EA but not in magnocellular SON/PVN; by 120 min SON/PVN were strongly Fos-positive. Confocal microscopy showed that ∼81% of Fos+ PKCδ/GluD1 EA neurons were surrounded by PACAP+ calyceal terminals, ∼88% of which co-expressed VGluT1. RNAscope revealed a selective KF Adcyap1/Slc17a7 population that became Fos-positive early. We conclude that KF PACAP/VGluT1 calyces onto PKCδ/GluD1 EA neurons provide a high-fidelity autonomic pathway that precedes vasopressin-mediated endocrine compensation.
Institution: Universidad Nacional Autónoma de México
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G1380686945
OpenAlex ID: W4416666171