# Inhibitory cell types and circuits in the lateral hypothalamus

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $396,157

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this proposal is to develop a circuit-level understanding of GABAergic neurons in the lateral
hypothalamic area (LHA) by resolving their molecular and functional diversity and local and long-range
connectivity. The LHA is a linchpin in the orchestration of fundamental aspects of behavior including arousal,
stress, feeding and motivated behavior. Owing to its unique position at the intersection of multiple neural and
humoral systems, the LHA drives essential behavioral programs that maintain homeostatic balance in physiology
and behavior. Underlying the diverse functions of the LHA is an exceptionally heterogeneous population of
neuronal cell types, of which few have been identified. Inhibitory GABAergic neurons in the LHA (LHAGABA) have
emerged as potent actuators of feeding, reward and stress. However, within this broad class of neurons lie poorly
resolved but functionally important subpopulations, which may differentially determine behavioral output.
Conventional methods are limited in their ability to decipher the molecular and functional diversity of LHAGABA
neurons, which represents a major barrier in our understanding of the role of LHA circuits in health and disease.
There is, therefore, a critical need to systematically delineate the neurochemical identity, cellular properties and
connectivity of functional subpopulations of LHAGABA neurons as a prerequisite to circuit-level behavioral
analyses. To fill this knowledge gap, we will establish the first large-scale and systematic molecular, cellular and
connectivity analysis of LHAGABA neurons at single-cell resolution using an integrated approach of
electrophysiological phenotyping, optogenetics-based circuit mapping and single-cell transcriptional profiling.
Our central hypothesis is that LHAGABA neurons can be classified into distinct functional subtypes according to
key molecular markers, electrical signatures and patterns of synaptic connectivity. We will probe this hypothesis
in three Specific Aims. Aim 1 will systematically define the electrophysiological and neuromodulatory phenotypes
of candidate LHAGABA neuron populations and refine these characteristics based on long-range projections to
the locus coeruleus (LC). Aim 2 will determine the synaptic connectivity between populations of LHAGABA neurons
and key, arousal-related targets, both within the LHA and the LC, using patch-clamp electrophysiology and
optogenetics. Aim 3 will apply cutting-edge quantitative single-cell transcriptional profiling methods to decipher
novel, molecularly distinct populations of LHAGABA neurons. Impact: As the first comprehensive neurochemical,
electrophysiological and anatomical census of inhibitory cell types in the LHA, this project will yield functional
subpopulations of LHAGABA neurons that, in turn, will allow the identification of key markers for the design of novel
cre driver lines and intersectional genetic tools for circuit-specific dissection of LHAGABA ci...

## Key facts

- **NIH application ID:** 9892042
- **Project number:** 5R01MH112739-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Alexander Choi Jackson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,157
- **Award type:** 5
- **Project period:** 2017-04-20 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892042

## Citation

> US National Institutes of Health, RePORTER application 9892042, Inhibitory cell types and circuits in the lateral hypothalamus (5R01MH112739-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9892042. Licensed CC0.

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