# Somatosensory and Autonomic Circuit Modulation by Brainstem Serotonergic Neurons

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2020 · $34,653

## Abstract

Serotonin (5-HT)-producing neurons projecting from brainstem to spinal cord (SC) are implicated in gating touch
and pain transmission and modulating physiological processes from cardiorespiratory control to
thermoregulation. Despite such vital and clinically significant roles, the specific serotonergic cells and SC circuits
involved are poorly understood, challenged by the formidable anatomy and lack of molecular genetic tools of
suitable specificity and resolving capacity. We have used intersectional genetic lineage tracing and
transcriptomics genome-wide to reveal subtypes of 5-HT neurons, now providing sought-after means to map
and functionally define the specific brainstem-SC circuits responsible for touch, pain, and homeostatic
modulation. We propose a model in which transcriptionally and molecularly distinct 5-HT subtypes form unique
projection patterns, selectively innervating regions of the spinal cord and modulating distinguishing sets of
downstream cellular partners, creating circuits, and thus, functions, unique to each 5-HT neuron subtype.
Intersectional labeling of 5-HT neuron subsets (Pet1+) identified by co-expression of Tachykinin1 (Tac1-Pet1
neurons) or Early growth response 2 (Egr2-Pet1 neurons) provides genetic access to two major caudal 5-HT
neuron subtypes for visualizing their precise innervation patterns along rostrocaudal and dorsoventral spinal cord
axes—previously unexplored. Further, because selective co-expression of neuromodulators distinguishes
different descending 5-HT neuron subtypes, I will explore the neurochemical composition of their axonal
terminals within the SC. To follow, I will use recently generated trans-synaptic tracing tools to visualize post-
synaptic partners of 5-HT neuron subtypes and combine intersectional optogenetic tools with acute SC slice
electrophysiology to probe the functional synaptic connectivity of Egr2-Pet1 and Tac1-Pet1 neuron descending
projections. Results will inform how genetically-defined 5-HT neuron subtypes are organized functionally
in the modulation of spinal cord circuits involved in sensory transmission or autonomic regulation.
Deliverables may include selective therapeutic substrates to treat pain, hyperesthesia, and cardiorespiratory
impairment.

## Key facts

- **NIH application ID:** 10268955
- **Project number:** 5F32NS106762-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Kathryn Michelle Lehigh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,653
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268955

## Citation

> US National Institutes of Health, RePORTER application 10268955, Somatosensory and Autonomic Circuit Modulation by Brainstem Serotonergic Neurons (5F32NS106762-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10268955. Licensed CC0.

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