# Central neuronal circuitry for homeostatic thermoregulation modulated by brain temperature

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $1,049,596

## Abstract

Project Summary/Abstract
 Maintenance of body temperature at the optimal level is crucial for survival, and it requires homeostatic
feedback regulation based on monitoring the temperature of internal organs as well as the environment.
Homeostatic thermoregulation in response to changes of brain temperature relies on the temperature-
sensitive neurons in the preoptic area of the anterior hypothalamus (POA). These neurons constitute about
one third of the medial and lateral POA neurons and are intermingled with temperature-insensitive neurons
that control drinking, feeding, sleep, and parental behaviors. For eight decades since the discovery of
temperature-sensitive neurons in the brain, electrophysiology has been the only way to identify these central
neurons. Having identified the first molecular marker for temperature-sensitive POA neurons by combining
single-cell RNA-seq with whole-cell patch-clamp recording, we will identify central neurons that are upstream
or downstream of these temperature-sensitive POA neurons, to elucidate the central neuronal circuitry for
thermoregulation.
 To identify central neurons that receive input from temperature-sensitive POA neurons, we will use
trans-synaptic tracers, and further verify these synaptic connections by using the PGDS Cre-line to drive
channelrhodopsin expression in temperature-sensitive POA neurons for optogenetic activation in brain slices.
 To test whether specific neuronal types in the suprachiasmatic nucleus (SCN) innervate temperature-
sensitive POA neurons to modulate the circadian variation of body temperature, we will use Cre-lines for
these SCN neuronal types to drive trans-synaptic tracer expression. We will also use these Cre-lines to drive
channelrhodopsin expression in SCN neurons, and record from POA neurons to determine whether they
receive SCN input and whether their firing rate changes when the temperature of the brain slice is altered.
 In addition to identifying central neurons that are upstream or downstream of temperature-sensitive
POA neurons, this proposed project includes mechanistic studies on the nature of the signals used by
temperature-sensitive POA neurons to alter the activity of their downstream neurons so as to modulate body
temperature, to test the hypothesis that, besides classical transmitters, endogenous PGD2 mediates
thermoregulation. These studies will generate predictive models at a conceptual level of understanding
thermoregulation.

## Key facts

- **NIH application ID:** 9970898
- **Project number:** 1RF1NS116588-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** LILY JAN
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,049,596
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970898

## Citation

> US National Institutes of Health, RePORTER application 9970898, Central neuronal circuitry for homeostatic thermoregulation modulated by brain temperature (1RF1NS116588-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970898. Licensed CC0.

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