# Developing Molecular and Computational Tools to Enable Visualization of Synaptic Plasticity In Vivo

> **NIH NIH RF1** · JOHNS HOPKINS UNIVERSITY · 2020 · $1,757,079

## Abstract

Project Summary
Developing new methodological and analytical tools to address currently insurmountable experimental questions
is crucial to the future of neuroscience. While recent advances in two-photon microscopy and activity sensors
have revolutionized our understanding of the cellular and circuit basis of behavior, many barriers still exist that
preclude fully exploring the molecular basis of these processes in vivo. This is an important question, as
modulating synaptic strength is thought to underlie higher brain functions such as learning and memory, whereas
synaptic degradation is observed in many neurological pathologies. Despite the clear significance of synaptic
communication, a large-scale analysis of how synapses across the brain are distributed and change during
learning has not been performed, mainly due to technical difficulties arising from the immensely complex nature
of synaptic networks. Here, we present a suite of novel methodologies that breaks through these barriers. Our
novel approach leverages CRISPR-based labeling of endogenous synaptic proteins, in vivo two-photon
microscopy to visualize fluorescently tagged synapses in behaving animals, and deep-learning-based automatic
synapse detection. Using these minimally invasive methods, we will be able to longitudinally track how the
strength of millions of individual synapses change during learning. By developing and enabling new strategies
to automatically detect and track vast numbers of synapses across entire brain regions, this pioneering approach
has the potential to provide us with an unprecedented view of synapses in behaving animals, enabling new
discoveries regarding how dynamic regulation of synaptic strength encodes learning and memory.

## Key facts

- **NIH application ID:** 10009886
- **Project number:** 1RF1MH123212-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Richard L Huganir
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,757,079
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009886

## Citation

> US National Institutes of Health, RePORTER application 10009886, Developing Molecular and Computational Tools to Enable Visualization of Synaptic Plasticity In Vivo (1RF1MH123212-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10009886. Licensed CC0.

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