# Cellular and molecular mechanisms that modulate synaptic function and plasticity

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $404,812

## Abstract

A gap in knowledge remains regarding how specific molecular changes that alter synaptic physiology actuate
particular behavioral preferences and memories in living animals. Knowledge on how the cell biology of
synapses is 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
overall objective of this proposal is to determine how C. elegans synapses between the thermosensory neuron
AFD and its only postsynaptic partner (AIY) are modified by experiences to express a learned temperature
preference. Our central hypothesis is that temperature preference memory is actuated in AFD through
presynaptic plasticity, which is in turn regulated through Protein Kinase C epsilon/eta (nPKCε)-dependent
mechanisms. Our hypothesis is based on our preliminary studies and published findings that indicate that
altering nPKCε activity in a single neuron (AFD) is sufficient to change the temperature preference of the
organism regardless of previous experience. We found that nPKCε localizes near presynaptic sites and alters
transmission of AFD sensory information to its postsynaptic partner (AIY). The rationale of the proposed aims
is that we can use the compact neural circuitry of C. elegans to dissect how conserved molecules, like nPKCε,
regulate presynaptic plasticity to modulate experience-dependent adaptive behaviors. We propose to use
genetic, cell biological, pharmacological, behavioral and calcium imaging approaches to achieve our three
specific aims: (1) Identify the role of nPKCε in modulating the AFD:AIY chemical synapse; (2) Identify the
molecular mechanisms that regulate nPKCε activation; and (3) Identify the presynaptic plasticity mechanism
regulated by nPKCε. Upon successful completion of the proposed aims we expect the contribution to be a
detailed molecular and cell biological understanding of how the temperature preference memory is actuated in
vivo through the regulation of presynaptic plasticity mediated by the conserved nPKCε pathways. The technical
and conceptual innovations in this proposal open up new horizons by providing access to the hubs of memory
actuation in living animals and with cell biological resolution. 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:** 10057395
- **Project number:** 5R01NS076558-09
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** DANIEL A COLON-RAMOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,812
- **Award type:** 5
- **Project period:** 2012-07-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057395

## Citation

> US National Institutes of Health, RePORTER application 10057395, Cellular and molecular mechanisms that modulate synaptic function and plasticity (5R01NS076558-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10057395. Licensed CC0.

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