# Molecular coordination of adhesion molecules in foraging behaviors and circuits

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2022 · $391,250

## Abstract

Project Summary/Abstract:
 We are using the small nematode C. elegans as an experimentally tractable model to
study the molecular roles of conserved genes in neuronal, circuit, and behavioral plasticity. We
aim to study the generation of behavior at a level and scope not possible in other organisms,
including parallel analysis of many genes across multiple behaviors and circuits. This includes
the goal of understanding the contribution and interactions of genes, and even single isoforms of
genes, in behavior. By focusing on conserved orthologs of genes associated with
neurodevelopmental and neuropsychiatric disorders, characterized by changes in behavior, we
hope to expand our understanding of the role of genes in behavior. Our molecular dissection of
gene function in single neurons between and across behavioral circuits has led to identification of
novel molecular mechanisms and genetic interactions in experience-dependent neuronal
plasticity and behavioral plasticity. Here we focus on synaptic cell adhesion molecule (sCAMs)
genes, including neurexins and neuroligins, which are extremely complex and redundant gene
families in vertebrates. The complexity and diversity of vertebrate neurons, circuits, and sCAM
genes have prevented simultaneous analysis at the genetic, molecular, circuit, and behavioral
resolution we hope to achieve. We propose to use C. elegans as a tractable experimental
system to simultaneously investigate the molecular and circuit mechanisms of many
synaptic adhesion genes in multiple behaviors. Our research plans over the coming years are
to expand the list of sCAM genes we are studying in depth to gain a more nuanced and complete
picture of the molecular coordination of sCAM genes in behavior. Using a suite of modern genetic
and neuroscience techniques we plan to 1) Identify networks of sCAM genes involved in multiple
foraging behaviors, 2) Define the cellular, subcellular, molecular, and temporal requirements of
each identified sCAM gene, and 3) Characterize the impact of each sCAM gene on the structure
and functional connectivity of a foraging circuit, all at single neuron resolution. Our top-down
approach relies heavily on using behavior as a readout of gene and circuit function, with the hope
this will provide a unique window into the genetic and molecular basis of behavior. Successful
completion of our work will result in a deeper understanding of the principles of neuronal circuit
formation, function, and behavioral output with implications across basic and disease-focused
disciplines. C. elegans are not only a uniquely tractable experimental model for the resolution of
experiments we propose, but also provide an inclusive experimental system to train/mentor
undergraduates, graduate students, and postdocs at all levels of experience.

## Key facts

- **NIH application ID:** 10498357
- **Project number:** 1R35GM146782-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael P Hart
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,250
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498357

## Citation

> US National Institutes of Health, RePORTER application 10498357, Molecular coordination of adhesion molecules in foraging behaviors and circuits (1R35GM146782-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498357. Licensed CC0.

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