# The neuropeptidergic connectome of Caenorhabitis elegant

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2021 · $479,769

## Abstract

Project Summary
A “connectome” describes the complete synaptic wiring diagram of a brain. The
elucidation of the connectome of any animal brain and, ultimately, the human brain will
have a tremendous impact on our understanding of brain function and constitutes a
central goal of 21st century neuroscience, akin to the efforts to assemble the complete
sequence of genomes. Current connectomic efforts are focused on determining the
anatomical synaptic connections between neurons in a brain, thereby completely
ignoring aspects of neuronal communication that are likely of equal importance but are
not captured by anatomical connections: Neuromodulatory communication by
neuropeptides and their cognate receptors. Neuropeptidergic communication is usually
non-synaptic, i.e. neuropeptides are often released from non-synaptic sites and cognate
neuropeptide receptors are often located distal from the source of the cognate
neuropeptide. While the importance of a number of neuropeptides and their receptors
in controlling behavior are well appreciated, the extent of usage of neuropeptidergic
signaling is only beginning to be fully appreciated. Every neuron in an animal nervous
system is now thought to express at least one neuropeptide, but the pathways of
communication of these neuropeptidergic signals have not been comprehensibly
mapped and, hence, our understanding of information flow in the nervous system
remains limited. We propose here to use C. elegans as a model system to establish the
first comprehensive neuropeptidergic connectome. The simplicity of the C. elegans
nervous system allows to undertake such a comprehensive analysis and, importantly,
allows to compare a neuropeptidergic connectome to that of the completely established
synaptic connectome. Based on preliminary data we expect to describe a “multilayer
connectome” with substantially distinct pathways of information flow, as well as distinct
and similar topological features. We will achieve to build such a connectome through (1)
comprehensively defining ligand/receptor pairs through in vitro receptor activation
assays, (2) defining the expression patterns of all neuropeptide and neuropeptide
receptor encoding genes, (3) synthesizing these data into a neuropeptidergic network
and computationally comparing the topology of this network to the synaptic
connectivity network and (4) undertaking a preliminary functional validation of specific
nodes and edges of this network.

## Key facts

- **NIH application ID:** 10202772
- **Project number:** 5R01NS110391-04
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Isabel Beets
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,769
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202772

## Citation

> US National Institutes of Health, RePORTER application 10202772, The neuropeptidergic connectome of Caenorhabitis elegant (5R01NS110391-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10202772. Licensed CC0.

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