# Cell-type-specific analysis of the suprachiasmatic nucleus

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $354,375

## Abstract

In mammals, behavioral and physiological processes display 24-hr rhythms that are controlled
by circadian oscillators located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN
acts as a master pacemaker at the top of a hierarchy of circadian oscillators distributed
throughout the body. Although the SCN is a relatively small nucleus in the brain containing
about 10,000 neurons on each side, it is composed of many cell types. Two major classes of
neuropeptide-containing neurons, VIP (vasoactive intestinal polypeptide) and AVP (arginine
vasopressin), are enriched in the “core” and the “shell” regions of the SCN, respectively. It is
known that the VIP and AVP neurons can subserve different functions, however, it has not been
possible to study genetically identified cell types in the SCN in real time at the cellular level.
 We have developed a new generation of bioluminescent circadian reporter mice that are
Cre-lox recombination dependent. Using cell-type-specific Cre drivers, these Cre-lox dependent
reporters can be activated in restricted and genetically defined cell populations so that circadian
properties of these cells can be studied separately from other cell types. In this proposal, we
will analyze the cell-type specific circadian properties of VIP and AVP neurons within the SCN
neuronal network by using a ColorSwitch PER2::LUCIFERASE reporter that has a click beetle
red (CBR) luciferase fused to PER2 that switches to a click beetle green (CBG) luciferase upon
Cre-lox recombination. With the cell-type restricted reporter, we can study for the first time the
circadian properties of each of these neuropeptide classes of neurons in the SCN.
 Here we will study the role of VIP and AVP neurons in controlling circadian behavioral
phenotypes using both loss-of-function and gain-of-function circadian mutations in these cell
classes. We will also use optogenetic control of VIP and AVP neurons to analyze the dynamics
of resetting within the SCN neuronal network. Finally, we will use single-cell RNA-seq of SCN
cells to classify SCN cell types and in labeled VIP and AVP neurons in order to determine the
molecular signatures and pathways characteristic of these two cell types. Together, these
experiments will provide critical new information on the circadian properties and dynamics of the
SCN in order to promote our understanding the circadian system in mammals, which is critical
for understanding how circadian disruption in humans contributes to morbidity associated with
neurological disorders, cognition, mental health, obesity, type 2 diabetes and cancer.

## Key facts

- **NIH application ID:** 10210449
- **Project number:** 5R01NS106657-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** JOSEPH S TAKAHASHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,375
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210449

## Citation

> US National Institutes of Health, RePORTER application 10210449, Cell-type-specific analysis of the suprachiasmatic nucleus (5R01NS106657-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10210449. Licensed CC0.

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