# DENDRITIC RELEASE OF NEUROPEPTIDES: ROLE IN BODILY HOMEOSTASIS

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2020 · $255,374

## Abstract

Bodily homeostasis involves orchestrated activities between hypothalamic autonomic and neuroendocrine
neuronal networks. Importantly, an imbalanced interaction between them constitutes the basis for
maladaptive responses (“neurohumoral activation”) observed in disease conditions (stress, heart failure and
the metabolic syndrome). Importantly, neurohumoral activation (which includes centrally driven sympathetic
activity and elevated circulating levels of vasopressin (VP)) directly correlates with prognosis, and mortality in
these diseases. Thus, understanding the mechanisms involved in autonomic and neuroendocrine integration,
both in health and disease conditions, is of critical physiological and clinical significance. The hypothalamic
paraventricular nucleus (PVN) plays a pivotal role in the generation of coordinated polymodal homeostatic
responses. Still, the mechanism by which the activity of these functionally distinct neuronal populations is
orchestrated during a homeostatic response remains elusive. We recently identified dendritic release of VP
from magnocellular neurosecretory neurons as a novel signaling mechanism underlying “wireless” (non-
synaptic) communication between neuroendocrine and presympathetic PVN neurons. We showed this
interpopulation crosstalk to play a major role coordinated neurosecretory/sympathetic homeostatic responses
to an osmotic challenge (OSM+). While significant progress has been obtained in our understanding of
mechanisms underlying activity-dependent release of neuropeptides from axonal terminals, limited information
is available regarding mechanisms regulating dendritic release, particularly during OSM+. Thus, we implemented a
highly innovative approach that enables us to quantitatively monitor dendritic VP release in real time, while
studying in a mechanistic manner the main processes involved in this interpopulation homeostatic crosstalk.
We obtained exciting preliminary data that supports our innovative hypothesis of a fine-tuned interplay
between glutamate NMDA receptors (NMDARs), backpropagating dendritic action potentials and K+ channels
in regulating dendritic VP release and neurosecretory-presympathetic signaling crosstalk in response to OSM+.
Moreover, we will test the hypothesis that astrocytes, recognized as key players in CNS function, exert a
pivotal influencing dendritic release of VP, its diffusing efficacy in the ECS, and ultimately, the generation of
multimodal homeostatic responses. These hypotheses will be tested in 3 specific aims: 1- To elucidate
mechanisms by which action potentials (APs) and NMDARs interact during OSM+ to evoke dendritic VP
release. 2- To elucidate mechanisms that regulate dendritic retrograde signaling and their impact on
dendritic release. 3- To elucidate mechanisms that control the diffusion of VP in the extracellular space,
influencing in turn its efficacy as an interpopulation signaling. We expect results from this work to broaden
our understanding of basic cellul...

## Key facts

- **NIH application ID:** 10003398
- **Project number:** 5R01NS094640-06
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Javier E Stern
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $255,374
- **Award type:** 5
- **Project period:** 2018-01-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003398

## Citation

> US National Institutes of Health, RePORTER application 10003398, DENDRITIC RELEASE OF NEUROPEPTIDES: ROLE IN BODILY HOMEOSTASIS (5R01NS094640-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003398. Licensed CC0.

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