# Understanding how the thermogenic response is orchestrated in the central nervous system

> **NIH NIH R00** · YALE UNIVERSITY · 2023 · $243,488

## Abstract

Thermogenesis is the principal mechanism through which mammals dissipate energy. Pioneering work dating
back to the 1930s demonstrated that neurons within the hypothalamus are sensitive to ambient and local
deviations in temperature, and that in turn, these neurons could outcome a potent change in body temperature.
A basic goal of neuroscience has been to identify the neural substrates underlying thermoregulation.
Significant progress has been made on understanding how hypothalamic cell types regulate thermogenesis
and thermogenesis related processes such as shivering; however, what populations outside of the
hypothalamus regulate temperature and how they accomplish this feat is incompletely understood.
 Mentored work will focus on establishing the dorsal raphe nucleus (DRN) as a critical regulator of
thermogenesis. In particular, we plan to delineate the neural circuits embedded within the DRN that regulate
energy expenditure through changes in thermogenesis. Preliminary data using whole-brain activity mapping,
demonstrate activation of GABAergic DRN neurons in heat environment. Furthermore, through a combination
of chemogenetic approaches, we proof that activation of these neurons directly regulate thermogenesis
through autonomic and/or behavioral mechanisms. Together, through a combination of functional, molecular,
and anatomic approaches, we will dissect whether the DRN bidirectionally controls thermogenesis and its
specific upstream and downstream neurocircuitry in thermal regulation. Previous identified roles in feeding
regulation for this region together with these results opens a new horizon in obesity treatment. On the
independent phase, I plan to identify the molecular identity of neurons in premotor areas of the CNS
responsible for a thermogenic response. My overarching hypothesis is that one subset of premotor
neurons in the CNS drives a coordinated response to control thermogenesis through sympathetic
nervous system mediated outflow to specific peripheral tissues. Furthermore, after corroborating that
direct modulation of these neurons modulates body temperature, the proposed research will focus on defining
if there is neuronal molecular heterogeneity in these premotor areas regarding the sympathetic nervous system
mediated coordinated thermogenic response. I will take an interdisciplinary approach, using a combination of
novel, state-of-the-art molecular technologies, such as optogenetics, neuronal tracing, calcium imaging and
molecular phenotyping, together with metabolic assessments. This work will ultimately identify how the CNS
orchestrates a thermogenic response. The proposed work will set the grounds for my own laboratory on central
nervous system (CNS) mediated regulation of thermogenesis. Altogether, this work seeks to better understand
thermogenesis regulation and establish the framework of my career as an independent investigator.
Additionally, future molecular profiling studies of these neurons will allow us to perform ce...

## Key facts

- **NIH application ID:** 10647872
- **Project number:** 5R00DK120869-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Marc Schneeberger
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $243,488
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10647872

## Citation

> US National Institutes of Health, RePORTER application 10647872, Understanding how the thermogenic response is orchestrated in the central nervous system (5R00DK120869-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10647872. Licensed CC0.

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