# Organization of Central Sympathic Pathways

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $504,699

## Abstract

Any condition that threatens homeostasis such as tissue injury, hemorrhage, hypoxia, infection,
hypothermia, or psychological stress elicits changes in autonomic nervous system (ANS)
function and specific behaviors. These changes can be beneficial for survival if transient but
pathogenic if sustained, as in hypertension. The main new idea tested is that C1 neurons, a
group of catecholaminergic/glutamatergic neurons within the rostral ventrolateral medulla of all
mammals, including humans, are a nodal point for expression of these stress responses. That
is, C1 neurons function like a switchboard enabling the expression of a large variety of ANS
responses to acute physical and psychological stresses mediated by both sympathetic and
parasympathetic divisions the ANS. The proposed experiments will use innovative methods
(e.g. intersectional genetics, optogenetics, pharmacogenetics) designed to test key aspects of
this theory, with particular emphasis on such novel topics as anti-inflammation, the prevention of
hypoxic tissue damage and behavioral effects elicited by C1 cell activation. This knowledge is
central to our understanding of how blood pressure and other physiological functions are
regulated by the autonomic nervous system in healthy, diseased or stressed states.
The specific aims tested are:
1: Is C1 cell stimulation sufficient to elicit physiological and behavioral signs of stress? Do C1
cells produce these effects by releasing glutamate or a catecholamine? Activation of C1 cells
with optogenetics in unanesthetized transgenic mice is expected to result in signs of stress.
2: Are C1 cells necessary for responses to physiological or psychological stressors?
Using loss of function optogenetics (archaerhodopsin) C1 cell activation is expected to be
necessary to maintain BP and HR in awake rats subjected to non-hypotensive hemorrhage,
hypoxia or bacterial infection. We will also test whether C1 cells are required for the autonomic
(e.g. cardiovascular, respiratory, GI and anti-inflammatory components) and behavioral
manifestations of restraint stress in conscious mice by either inhibiting (pharmacogenetically) or
selectively destroying these neurons.
3: Which C1 cells regulate blood pressure? Using mouse intersectional genetics and Boolean
vectors, subgroups of C1 cells defined by peptide expression or CNS projection will be
transduced to selectively express ChannelRhodopsin2. These subgroups are expected to have
distinct projections and their optogenetic activation is expected to elicit highly specific
physiological and behavioral responses.

## Key facts

- **NIH application ID:** 9850614
- **Project number:** 5R01HL028785-37
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** RUTH L STORNETTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,699
- **Award type:** 5
- **Project period:** 1989-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850614

## Citation

> US National Institutes of Health, RePORTER application 9850614, Organization of Central Sympathic Pathways (5R01HL028785-37). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9850614. Licensed CC0.

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