# Examination of the cell biology of the synapse and behavior

> **NIH NIH R35** · YALE UNIVERSITY · 2024 · $1,195,932

## Abstract

PROJECT SUMMARY
A gap in knowledge remains regarding how structural organization of synapses, robustly established during
development, is also flexibly modified during learning to sustain behaviors. Knowledge on how the cell biology
of synapses is established and altered in the actuation of memories is of critical importance in our aspiration to
understand how the building blocks of the nervous system come together to produce its functional output,
behaviors. The key scientific premise of my research program is that our understanding of how complex
behaviors emanate from the molecular building blocks of synapses could be meaningfully expanded by
simultaneously interrogating structure-function relationships across scales, bridging knowledge on the molecular
composition of individual synapses within single cells, the organization of single cells within circuits, and the
coordinated activity of circuits within the brain of behaving animals. Achieving this integrated view is a challenge
of critical importance best summarized in the BRAIN Working Group Report to the NIH Director, and requires
new approaches that allow the integration of knowledge across 1) spatial scales, from the subcellular architecture
of the synapse to the cellular architecture of the circuits governing behaviors, and 2) temporal scales, from the
events leading to synaptic assembly during development, to the events leading to synaptic plasticity during
learned behaviors. To address this challenge, my lab established strategic collaborations with network scientists,
microscopists and computational biologists and pioneered integrated approaches that enable unprecedented
access to the cell biology of the synapse in the thermotaxis circuit of C. elegans. Using these approaches we
discovered concepts that reframed how we understand the cell biology of the synapse in vivo, and now position
us to address three fundamental questions in neuroscience: 1) How is synaptic specificity achieved during the
development of the nerve ring neuropil? 2) How are changing metabolic needs met at synapses to sustain
function? 3) How are synapses modified to form memories and underpin behaviors? We propose to answer
these questions for the thermotaxis circuit to define fundamental mechanisms that govern how synapses are
precisely assembled, maintained, and modified to sustain behavior. Importantly, the resulting integrated
understanding across scales will yield new concepts regarding the interplay between the programs that robustly
establish synaptic architecture during development, and the plasticity programs that govern synaptic change to
facilitate behavior. We anticipate, because of the molecular conservation of the examined pathways, that
advancements in our understanding based on these innovations will result in transposable lessons of broad
biological significance.

## Key facts

- **NIH application ID:** 10835035
- **Project number:** 5R35NS132156-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** DANIEL A COLON-RAMOS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,195,932
- **Award type:** 5
- **Project period:** 2023-05-01 → 2031-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835035

## Citation

> US National Institutes of Health, RePORTER application 10835035, Examination of the cell biology of the synapse and behavior (5R35NS132156-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10835035. Licensed CC0.

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