# The role of presynaptic C1QL3 in a hypothalamic arousal circuit

> **NIH NIH F31** · UNIVERSITY OF CONNECTICUT STORRS · 2023 · $47,694

## Abstract

PROJECT SUMMARY:
Narcolepsy with cataplexy is a debilitating neurological disorder that results in sleep attacks during the day and
fragmented sleep at night. This condition is associated with the loss of hypocretin/orexin (HCRT/OX) neurons in
the lateral hypothalamic area (LHA), which are important regulators of sleep/wake behavior and arousal states.
Despite a broad array of work investigating HCRT/OX neuron function in physiology and behavior, comparatively
little is known about the molecular mechanisms underlying their synaptic structure and function. Based on the
results of our lab’s recent single cell RNA sequencing (scRNA-seq) analysis of the LHA, we propose that C1ql3,
encoding C1QL3, a previously described excitatory synapse organizing protein in other brain regions, may
likewise be an important element in excitatory synaptic transmission in HCRT/OX neurons, and help us shed
light on the molecular components of these important arousal-regulating synapses. To test this, I will confirm the
expression of C1ql3 and its gene product C1QL3 in HCRT/OX neurons, at both the mRNA and protein levels
(Aim 1). I will then conditionally knock out the C1ql3 gene in HCRT/OX neurons to determine the consequences
of its deletion on HCRT/OX synaptic structure and function (Aim 2), as well as its potential importance for
HCRT/OX neuron function in promoting arousal (Aim 3). This work will have several important outcomes,
including 1) identifying the role of a novel genetic marker in HCRT/OX neurons, 2) informing us of the importance
of C1QL3 in synaptic function and behavior relating to HCRT/OX neurons, and 3) provide me with training in
neuroscience techniques ranging from cellular and molecular to behavioral to enable me to become a more well-
rounded scientist and scientific communicator, as I pursue my goal of becoming an independent researcher.

## Key facts

- **NIH application ID:** 10778192
- **Project number:** 5F31HL165896-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** William Patrick Armstrong
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 5
- **Project period:** 2022-08-19 → 2026-08-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778192

## Citation

> US National Institutes of Health, RePORTER application 10778192, The role of presynaptic C1QL3 in a hypothalamic arousal circuit (5F31HL165896-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10778192. Licensed CC0.

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