# The Effect of Sleep on Neural Circuit Connections

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $4,711

## Abstract

Project Summary/Abstract
A fundamental question in neuroscience and human health is how do different brain states alter neuronal
connections and how are these changes carried out at the cellular and molecular levels? We propose to
address this question by examining neuronal connections through out the compact, completely described
nervous system of the transparent nematode C. elegans as its whole brain activity cycles between
wakefulness and sleep. Specifically, we propose to use our ability to modulate the C. elegans brain state to
examine how the structure and function of excitatory as well as inhibitory synapses are changed as a function
of recurrent neural activity. Further, we will identify the molecular mechanisms by which this is achieved. In
Aim 1, We will ask how the brain states affect synaptic architecture across the animal's nervous system by
testing different types of connections throughout the animals for their response to wakefulness and sleep. We
will then ask whether the number or size of connections is affected. We will also identify the molecular
regulators of the brain state-dependent synaptic changes, and visualize synaptic components in each brain
state to determine how and when synapses are altered. These studies would provide the first evidence of
broad sleep-dependent synaptic remodeling in C. elegans. In Aim 2, We will characterize the activity calcium
transients (GCaMP6/7), cGMP fluxes (WincG) and neuropeptide-driven GPCR ligand binding (D-lite adapted
reporters) of the entire brain of C. elegans as it sleeps and compare that to the wakeful animal. Using this
information we will assess the pattern of these changes and relate them to the structure of synaptic
components within the units that change most. We will attempt to understand if the synaptic changes are
dispersed brain-wide and whether these connections are responsible for stabilizing sleep dependent changes
in behavior. We will then alter the brain activity using optical manipulation of ChR, Arch, our cGMP-sponge
WincD and cell and timing specific regulation of neuropeptide processing during sleep to test the requirement
for patterned activity to direct changes in connections that we observe. In this way, we will begin to understand
how brain state effects structural changes that affect behavior. These studies would provide the first brain wide
understanding of the interplay between the activity and structure of connections in any animal. This
understanding will provide insights into novel approaches to therapies aimed at mitigating activity-driven
changes in human brain activity that promote maladaptive responses to activity such as addiction and post
traumatic stress disorder.

## Key facts

- **NIH application ID:** 10444697
- **Project number:** 3R01NS087544-08S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Noelle D L 'Etoile
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $4,711
- **Award type:** 3
- **Project period:** 2014-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444697

## Citation

> US National Institutes of Health, RePORTER application 10444697, The Effect of Sleep on Neural Circuit Connections (3R01NS087544-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10444697. Licensed CC0.

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