A neural circuit for flexible control of persistent behavioral states
- Massachusetts Institute of Technology, United States
Abstract
To adapt to their environments, animals must generate behaviors that are closely aligned to a rapidly changing sensory world. However, behavioral states such as foraging or courtship typically persist over long time scales to ensure proper execution. It remains unclear how neural circuits generate persistent behavioral states while maintaining the flexibility to select among alternative states when the sensory context changes. Here, we elucidate the functional architecture of a neural circuit controlling the choice between roaming and dwelling states, which underlie exploration and exploitation during foraging in C. elegans. By imaging ensemble-level neural activity in freely-moving animals, we identify stereotyped changes in circuit activity corresponding to each behavioral state. Combining circuit-wide imaging with genetic analysis, we find that mutual inhibition between two antagonistic neuromodulatory systems underlies the persistence and mutual exclusivity of the neural activity patterns observed in each state. Through machine learning analysis and circuit perturbations, we identify a sensory processing neuron that can transmit information about food odors to both the roaming and dwelling circuits and bias the animal towards different states in different sensory contexts, giving rise to context-appropriate state transitions. Our findings reveal a potentially general circuit architecture that enables flexible, sensory-driven control of persistent behavioral states.
Data availability
Code has been made available on Github. Data has been made available on Dryad.
-
A neural circuit for flexible control of persistent behavioral statesDryad Digital Repository, doi:10.5061/dryad.3bk3j9kh3.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01NS104892)
- Steven W Flavell
National Science Foundation (IOS 1845663)
- Steven W Flavell
National Science Foundation (DUE 1734870)
- Steven W Flavell
JPB Foundation (PIIF)
- Steven W Flavell
JPB Foundation (PNDRF)
- Steven W Flavell
Brain and Behavior Research Foundation (NARSAD Young Investigator Award)
- Steven W Flavell
McKnight Foundation (McKnight Scholars Award)
- Steven W Flavell
JPB Foundation (Picower Fellowship)
- Ni Ji
Alfred P. Sloan Foundation (Sloan Research Fellowship)
- Steven W Flavell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Manuel Zimmer, University of Vienna, Austria
Version history
- Preprint posted: February 5, 2020 (view preprint)
- Received: September 7, 2020
- Accepted: November 17, 2021
- Accepted Manuscript published: November 18, 2021 (version 1)
- Version of Record published: December 9, 2021 (version 2)
Copyright
© 2021, Ji et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,679
- views
-
- 688
- downloads
-
- 33
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A neural circuit for flexible control of persistent behavioral states
eLife 10:e62889.
https://doi.org/10.7554/eLife.62889
Further reading
-
- Neuroscience
Vesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here, we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.
-
- Evolutionary Biology
- Neuroscience
Neuropeptides are ancient signaling molecules in animals but only few peptide receptors are known outside bilaterians. Cnidarians possess a large number of G protein-coupled receptors (GPCRs) – the most common receptors of bilaterian neuropeptides – but most of these remain orphan with no known ligands. We searched for neuropeptides in the sea anemone Nematostella vectensis and created a library of 64 peptides derived from 33 precursors. In a large-scale pharmacological screen with these peptides and 161 N. vectensis GPCRs, we identified 31 receptors specifically activated by 1 to 3 of 14 peptides. Mapping GPCR and neuropeptide expression to single-cell sequencing data revealed how cnidarian tissues are extensively connected by multilayer peptidergic networks. Phylogenetic analysis identified no direct orthology to bilaterian peptidergic systems and supports the independent expansion of neuropeptide signaling in cnidarians from a few ancestral peptide-receptor pairs.
