# CHANGE OF GRANTEE INSTITUTION:  Autophagy Underlies Synaptic Development and ASDs-Related Social Deficits During Critical Period

> **NIH NIH R21** · CLEVELAND STATE UNIVERSITY · 2020 · $423,302

## Abstract

PROJECT SUMMARY/ABSTRACT
During the critical period of brain development, sensory stimuli induce remodeling of cortical synapses by
eliminating immature synapses, while strengthening others. Deficits of sensory-dependent synaptic remodeling
are thought to underlie the delayed maturation of synapses and imbalance in excitation/inhibition, which
underlies hypersensitivity to sensory stimuli and deficits of social behaviors associated with autism and other
neuropsychiatric disorders. However, knowledge about how sensory input drives synaptic remodeling is still
unmet. Autophagy is a process of programmed degradation and recycling of cellular components via the
lysosomal pathway in neurons and other cells and is involved in presynaptic function, synapse elimination and
synaptic plasticity in neurons. Our preliminary findings with mouse model indicated that sensory deprivation by
trimming whiskers downregulates autophagy in somatosensory neurons, increases the synapse numbers, and
leads to sensory and social deficits in adulthood. The objective of this research is to document a role of
autophagy in sensory experience-induced remodeling of synapse and its importance on sensory processing and
sociability in heathy and diseases. Fragile X syndrome (FXS) is the leading genetic cause of autism, which is
associated with hypersensitivity and social deficits. Our preliminary finding that autophagy is decreased in
somatosensory cortex of FXS mice suggests that impaired autophagy might be causally related to aberrant
synaptic remodeling, as well as the behavioral deficits in adult FXS mice. The underlying hypothesis of this
project is that sensory stimuli induce autophagy, and that autophagy is critical to experience-dependent synaptic
remodeling during the critical period, which subsequently affect sensory processing and social interactions in
adulthood. We further postulate that in FXS mice, while impaired autophagy causes aberrant synaptic
remodeling, hypersensitivity and social deficits, activation of autophagy can rescue these disorders. We seek to
test this hypothesis in the following: Aim 1. Document a role of autophagy in sensory experience-dependent
synapse remodeling, sensory processing and social behaviors. Experiments will: 1) test whether sensory
deprivation during the critical period suppress autophagy in somatosensory cortex neurons of wild-type mice; 2)
establish that autophagy is critical for sensory-dependent synapse remodeling during the critical period, as well
as the correct sensory processing and sociability in adult mice.; and 3) determine that mimicking sensory
stimulation with a chemogenetic approach, DREADDS, rescues autophagy, sensory processing and social
interactions in sensory-deprived mice. Aim 2. Study the role of autophagy in deficits of sensory processing
and social interactions in Fragile X mice. Experiments will: 1) examine whether impaired autophagy is causally
related to the deficits of synapse remodeling in somatosensory c...

## Key facts

- **NIH application ID:** 10356983
- **Project number:** 7R21NS118378-02
- **Recipient organization:** CLEVELAND STATE UNIVERSITY
- **Principal Investigator:** Jingqi Yan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,302
- **Award type:** 7
- **Project period:** 2021-03-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356983

## Citation

> US National Institutes of Health, RePORTER application 10356983, CHANGE OF GRANTEE INSTITUTION:  Autophagy Underlies Synaptic Development and ASDs-Related Social Deficits During Critical Period (7R21NS118378-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356983. Licensed CC0.

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