# Mechanisms of Silent Synapse Maturation for Excitatory Network Refinement

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $414,650

## Abstract

Abstract
Silent synapses are instrumental in experience-dependent cortical network reorganization. This process is
particularly prevalent during developmental critical periods when silent synapses are abundant. Genesis, loss,
and maturation of these silent synapses alters the synaptic connection pattern to establish the fundamental
processing architectures of excitatory neural networks during critical periods. Whether silent synapses mature
or are lost is a critical decision point to determine the fate of synaptic connections between neurons. Thus, the
delicate balance of the pace of silent synapse maturation and their loss determines the outcome of the refinement
process during critical periods. However, the molecular underpinnings regulating the pace of silent synapse
maturation and how changes in pace impact local neural circuits and sensory perception remains elusive. Our
previous studies report that the pace is controlled by the opposing but cooperative function of two postsynaptic
signaling scaffolds, PSD-93 and -95, that inhibits and promotes silent synapse maturation, respectively. Using
unbiased quantitative phosphoproteomic approaches, we identified signaling pathways affected by PSD-93 and
-95 that govern the maturation. The proposed experiments employ genetic manipulations using viral vectors and
transgenic mouse models, combined with electrophysiological analysis, quantitative proteomic analyses, and
confocal imaging to focus on a fundamentally new concept of silent-synapse based mechanism driving
experience-dependent cortical development. Results will reveal a so far unknown signaling mechanism in
regulating the pace of silent synapse maturation. Expected results will advance our understanding of the
molecular mechanisms of neural network refinement, and their impact on local circuits and visual perception,
exemplified in the primary visual cortex, but relevant to cortical networks in general.

## Key facts

- **NIH application ID:** 10812571
- **Project number:** 1R01MH131717-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Wilhelm Haas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $414,650
- **Award type:** 1
- **Project period:** 2024-08-06 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812571

## Citation

> US National Institutes of Health, RePORTER application 10812571, Mechanisms of Silent Synapse Maturation for Excitatory Network Refinement (1R01MH131717-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10812571. Licensed CC0.

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