# Deconstructing the sertonin system in the mouse brain

> **NIH NIH RF1** · STANFORD UNIVERSITY · 2023 · $2,164,186

## Abstract

PROJECT SUMMARY
Serotonin is an evolutionarily conserved neurotransmitter that modulates the activity of excitatory and
inhibitory neurons throughout the entire mammalian brain and is thus essential for diverse aspects of
physiology and behavior. Drugs that impact the serotonin system have been used to treat numerous brain
disorders including depression, anxiety, and post-traumatic stress disorder. In the mammalian brain,
serotonin neurons are clustered in the raphe nuclei of the brainstem, but project axons across the entire
brain. We lack a fundamental understand of how serotonin neurons are organized to achieve their diverse
functions.
 Our recent studies suggested that dorsal raphe (DR) serotonin neurons likely comprise parallel
subsystems with distinct projection patterns, input biases, physiological response properties, and
behavioral functions. For example, DR serotonin neurons that project to orbitofrontal cortex and central
amygdala have distinct collateralization patterns, receive quantitatively biased monosynaptic inputs from
a diverse set of brain regions, respond oppositely to punishment, and have distinct functions in promoting
active coping and anxiety behaviors, respectively. Single-cell transcriptomic profiling revealed that DR
serotonin neurons comprise 7 transcriptomic types, distinct from the 4 transcriptomic types in the nearby
median raphe (MR) serotonin neurons. Our unpublished data on collateralization mapping further indicated
diverse, complex, yet stereotyped collateralization patterns of DR and MR serotonin neurons.
 Here we propose to use a combination of approaches, including viral-genetic access of serotonin
neurons that project to specific brain regions, whole-brain mapping of axon collateralization patterns, in
situ transcriptomic and projectomic typing, chemogenetic and optogenetic manipulations, fiber photometry
and Neuropixels-based physiological recordings, and statistical modeling. Specifically, we will complete
the collateralization mapping and divide serotonin neurons into specific subsystems. We will determine the
behavioral functions of a subset of serotonin systems. We will also characterize the dynamics of a subset
of serotonin subsystems and the effect of their action on target neuron dynamics. By combining viral
genetic dissection of serotonin subsystems with anatomical, physiological, and behavioral analyses, our
proposed studies have the potential to take a major step forward in our understanding of the organization
and function of the serotonin system in the mammalian brain.

## Key facts

- **NIH application ID:** 10656870
- **Project number:** 1RF1NS131987-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** LIQUN LUO
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,164,186
- **Award type:** 1
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656870

## Citation

> US National Institutes of Health, RePORTER application 10656870, Deconstructing the sertonin system in the mouse brain (1RF1NS131987-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10656870. Licensed CC0.

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