# Experience-Dependent Reorganization of Excitatory Synapse Connectivity

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $605,149

## Abstract

Project Summary 
Optimal refinement of neural circuits during development is a highly controlled process that depends critically on 
experience. Ample genetic evidence in mental disorders points specifically to defects in molecular targets related 
to experience-­dependent developmental plasticity of excitatory synapses, and dysregulation of this fundamental 
developmental process results in a variety of neuropsychiatric diseases. This project seeks to elucidate 
mechanisms by which experience sculpts the functional connection of excitatory synapses during development 
and how perturbations in this process can derail the normal developmental trajectory. We found that during the 
critical period of their functional maturation, excitatory synapses of the mouse primary visual cortex (V1) maintain 
a dynamic equilibrium in their AMPA receptor-­mediated transmission. This equilibrium requires neurogranin (Ng), 
a  postsynaptic calmodulin-­binding protein  important  for  synaptic  plasticity, which is has been implicated in 
schizophrenia and mental retardation. Our preliminary studies show that in addition to controlling incorporation 
of  AMPA  receptors  into  AMPA  receptor-­lacking (silent) synapses and synaptic pruning, Ng levels also control 
the timing of the developmental switch in NMDA receptor subunits, and change the phosphorylation profiles of 
several post synaptic proteins including NMDA receptor and PSD-­93/95. This project investigates the hypothesis 
that Ng levels influence the experience-­dependent reorganization of excitatory synaptic connectivity by altering 
Ca/CaM-­dependent  signaling  pathways, including  PP2B  and  NMDA  receptors, using a combination of virus-­
mediated gene manipulation, synaptic physiology, channel biophysics, morphological analysis, and behavioral 
interrogation. The results will elucidate the molecular pathways governing experience-­dependent refinement of 
excitatory synaptic connectivity during development and will help to identify potential targets for pharmacologic 
interventions in patient with neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10408706
- **Project number:** 5R01MH118298-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jen Qian Pan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $605,149
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408706

## Citation

> US National Institutes of Health, RePORTER application 10408706, Experience-Dependent Reorganization of Excitatory Synapse Connectivity (5R01MH118298-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10408706. Licensed CC0.

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