# The Function of Sleep in Critical Period Plasticity

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2024 · $95,690

## Abstract

Project Summary
Although we spend a third of our lives sleeping, the function of this evolutionarily conserved behavior
remains elusive. Most studies investigating the function of sleep have focused on sleep in adults.
However, young animals spend an even greater proportion of their lives asleep, and their sleep is
deeper and has distinct electrophysiological features. Sleep in young animals is thought to aid brain
development by promoting plasticity. These plastic processes occur during critical periods in which
neural circuits are shaped by experience. Yet, the molecular, cellular and circuit mechanisms by
which sleep functions in critical period plasticity remains elusive. This proposal aims to address this
question by using a simple neural circuit in a genetically tractable model organism. In Aim 1, I will
define sleep substages using behavioral features and statistical modeling, as well as imaging
methods, and then determine if critical period plasticity requires a specific form of sleep. In Aim 2, I
will investigate the neurophysiological processes by which sleep promotes critical period plasticity
using patch clamp electrophysiology and investigate the genes that are important for this process
using single cell RNA sequencing. In Aim 3, I will perform a large-scale RNAi screen using a
behavioral assay to find novel genes that are involved in sleep-dependent critical period plasticity. In
addition, I will investigate whether sleep-related neural activity is generated by astrocytes to aid
critical period plasticity. Overall, these aims will delineate the function of specific sleep states in young
animals and identify cellular and molecular mechanisms underlying sleep-dependent critical period
plasticity. Because sleep disturbances in early life are predictors of neurocognitive disorders such as
autism and attention deficit disorders, this work may have implications for the treatment of
neurodevelopmental conditions. To achieve these aims, I have brought together a mentoring team
which includes experts in computational modeling, transcriptional profiling, and developmental neural
plasticity. In addition, the proposed career development and research plan will capitalize on the
exceptional environment, facilities, and resources that Johns Hopkins University provides. My
overarching career goal is to obtain a tenure track faculty position and establish my own research
program as an independent scientist, and the proposed work and training will form a strong
foundation for achieving this goal.

## Key facts

- **NIH application ID:** 10768720
- **Project number:** 5K99NS124976-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MEHMET KELES
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $95,690
- **Award type:** 5
- **Project period:** 2023-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768720

## Citation

> US National Institutes of Health, RePORTER application 10768720, The Function of Sleep in Critical Period Plasticity (5K99NS124976-02). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10768720. Licensed CC0.

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