Cargando…

A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans

Alcohol intoxication can impact learning and this may contribute to the development of problematic alcohol use. In alcohol (ethanol)-induced state-dependent learning (SDL), information learned while an animal is intoxicated is recalled more effectively when the subject is tested while similarly into...

Descripción completa

Detalles Bibliográficos
Autores principales: Lindsay, Jonathan H., Mathies, Laura D., Davies, Andrew G., Bettinger, Jill C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674237/
https://www.ncbi.nlm.nih.gov/pubmed/36343256
http://dx.doi.org/10.1073/pnas.2210462119
_version_ 1784833112355635200
author Lindsay, Jonathan H.
Mathies, Laura D.
Davies, Andrew G.
Bettinger, Jill C.
author_facet Lindsay, Jonathan H.
Mathies, Laura D.
Davies, Andrew G.
Bettinger, Jill C.
author_sort Lindsay, Jonathan H.
collection PubMed
description Alcohol intoxication can impact learning and this may contribute to the development of problematic alcohol use. In alcohol (ethanol)-induced state-dependent learning (SDL), information learned while an animal is intoxicated is recalled more effectively when the subject is tested while similarly intoxicated than if tested while not intoxicated. When Caenorhabditis elegans undergoes olfactory learning (OL) while intoxicated, the learning becomes state dependent such that recall of OL is only apparent if the animals are tested while intoxicated. We found that two genes known to be required for signal integration, the secreted peptide HEN-1 and its receptor tyrosine kinase, SCD-2, are required for SDL. Expression of hen-1 in the ASER neuron and scd-2 in the AIA neurons was sufficient for their functions in SDL. Optogenetic activation of ASER in the absence of ethanol during learning could confer ethanol state dependency, indicating that ASER activation is sufficient to signal ethanol intoxication to the OL circuit. To our surprise, ASER activation during testing did not substitute for ethanol intoxication, demonstrating that the effects of ethanol on learning and recall rely on distinct signals. Additionally, intoxication-state information could be added to already established OL, but state-dependent OL did not lose state information when the intoxication signal was removed. Finally, dopamine is required for state-dependent OL, and we found that the activation of ASER cannot bypass this requirement. Our findings provide a window into the modulation of learning by ethanol and suggest that ethanol acts to modify learning using mechanisms distinct from those used during memory access.
format Online
Article
Text
id pubmed-9674237
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-96742372022-11-19 A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans Lindsay, Jonathan H. Mathies, Laura D. Davies, Andrew G. Bettinger, Jill C. Proc Natl Acad Sci U S A Biological Sciences Alcohol intoxication can impact learning and this may contribute to the development of problematic alcohol use. In alcohol (ethanol)-induced state-dependent learning (SDL), information learned while an animal is intoxicated is recalled more effectively when the subject is tested while similarly intoxicated than if tested while not intoxicated. When Caenorhabditis elegans undergoes olfactory learning (OL) while intoxicated, the learning becomes state dependent such that recall of OL is only apparent if the animals are tested while intoxicated. We found that two genes known to be required for signal integration, the secreted peptide HEN-1 and its receptor tyrosine kinase, SCD-2, are required for SDL. Expression of hen-1 in the ASER neuron and scd-2 in the AIA neurons was sufficient for their functions in SDL. Optogenetic activation of ASER in the absence of ethanol during learning could confer ethanol state dependency, indicating that ASER activation is sufficient to signal ethanol intoxication to the OL circuit. To our surprise, ASER activation during testing did not substitute for ethanol intoxication, demonstrating that the effects of ethanol on learning and recall rely on distinct signals. Additionally, intoxication-state information could be added to already established OL, but state-dependent OL did not lose state information when the intoxication signal was removed. Finally, dopamine is required for state-dependent OL, and we found that the activation of ASER cannot bypass this requirement. Our findings provide a window into the modulation of learning by ethanol and suggest that ethanol acts to modify learning using mechanisms distinct from those used during memory access. National Academy of Sciences 2022-11-07 2022-11-15 /pmc/articles/PMC9674237/ /pubmed/36343256 http://dx.doi.org/10.1073/pnas.2210462119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Lindsay, Jonathan H.
Mathies, Laura D.
Davies, Andrew G.
Bettinger, Jill C.
A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title_full A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title_fullStr A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title_full_unstemmed A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title_short A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans
title_sort neuropeptide signal confers ethanol state dependency during olfactory learning in caenorhabditis elegans
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674237/
https://www.ncbi.nlm.nih.gov/pubmed/36343256
http://dx.doi.org/10.1073/pnas.2210462119
work_keys_str_mv AT lindsayjonathanh aneuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT mathieslaurad aneuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT daviesandrewg aneuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT bettingerjillc aneuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT lindsayjonathanh neuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT mathieslaurad neuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT daviesandrewg neuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans
AT bettingerjillc neuropeptidesignalconfersethanolstatedependencyduringolfactorylearningincaenorhabditiselegans