# Powering the Brain: the Cell Biology of Neuroenergetics

> **NIH NIH DP1** · YALE UNIVERSITY · 2020 · $1,172,500

## Abstract

Project Summary
 Synapses are conserved structures that govern information flow through neural circuits. My laboratory is
interested in understanding how synapses are assembled and maintained in vivo to build the circuits that
underlie behavior, and how they are modified to store memories. We recently made an unexpected discovery
that is orthogonal to our research program and reframes our understanding of the principles governing synaptic
function. We discovered that during energy stress, glycolytic proteins in C. elegans dynamically relocalize to
synapses to meet local energy demands and power the synaptic vesicle cycle. Our findings underscore an
important relationship between individual synapses and their local energy environments. Based on these
findings we propose the bold hypothesis that local regulation of energy metabolism underlies the plastic
properties of specific neurons and synapses, thereby governing circuit function and animal behavior.
 Our proposed hypothesis is unconventional. While functional magnetic resonance spectroscopy studies
have demonstrated that brain metabolism is tightly linked to neuronal function at a circuit level, how energy
metabolism is regulated at a subcellular level is not understood, or considered in the context of synaptic
physiology and plasticity. Could energy metabolism be compartmentalized within cells to preferentially power
specific cellular functions? Could local regulation of energy flow within neurons (neuroenergetics) restrict, or
potentiate, information processing and circuit function? Understanding how neuroenergetics is locally regulated
within neurons could be paradigm shifting, reframing our knowledge regarding the mechanisms that regulate
synaptic function, both in physiology and in disease.
 In this Pioneer proposal, we rigorously examine our hypothesis with new cell biological probes to be used
in vivo, in specific neurons and in behaving C. elegans to understand neuroenergetics in single synapses. We
examine how membrane-less metabolic subcompartments form through liquid-phase transition, and the
physiological implications of their localization to subcellular regions. Completion of the proposed work could
have impact beyond the field of neuroscience, as it could broadly reframe the importance of local metabolism
and its functional role in meeting local energy demands in cells.

## Key facts

- **NIH application ID:** 10001621
- **Project number:** 5DP1NS111778-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** DANIEL A COLON-RAMOS
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,172,500
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001621

## Citation

> US National Institutes of Health, RePORTER application 10001621, Powering the Brain: the Cell Biology of Neuroenergetics (5DP1NS111778-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10001621. Licensed CC0.

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