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Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal

Projections from the lateral habenula (LHb) control ventral tegmental area (VTA) neuronal populations’ activity and both nuclei shape the pathological behaviors emerging during cocaine withdrawal. However, it is unknown whether cocaine withdrawal modulates LHb neurotransmission onto subsets of VTA n...

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Autores principales: Clerke, Joseph, Preston-Ferrer, Patricia, Zouridis, Ioannis S., Tissot, Audrey, Batti, Laura, Voigt, Fabian F., Pagès, Stephane, Burgalossi, Andrea, Mameli, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044201/
https://www.ncbi.nlm.nih.gov/pubmed/33867967
http://dx.doi.org/10.3389/fnsyn.2021.643138
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author Clerke, Joseph
Preston-Ferrer, Patricia
Zouridis, Ioannis S.
Tissot, Audrey
Batti, Laura
Voigt, Fabian F.
Pagès, Stephane
Burgalossi, Andrea
Mameli, Manuel
author_facet Clerke, Joseph
Preston-Ferrer, Patricia
Zouridis, Ioannis S.
Tissot, Audrey
Batti, Laura
Voigt, Fabian F.
Pagès, Stephane
Burgalossi, Andrea
Mameli, Manuel
author_sort Clerke, Joseph
collection PubMed
description Projections from the lateral habenula (LHb) control ventral tegmental area (VTA) neuronal populations’ activity and both nuclei shape the pathological behaviors emerging during cocaine withdrawal. However, it is unknown whether cocaine withdrawal modulates LHb neurotransmission onto subsets of VTA neurons that are part of distinct neuronal circuits. Here we show that, in mice, cocaine withdrawal, drives discrete and opposing synaptic adaptations at LHb inputs onto VTA neurons defined by their output synaptic connectivity. LHb axons innervate the medial aspect of VTA, release glutamate and synapse on to dopamine and non-dopamine neuronal populations. VTA neurons receiving LHb inputs project their axons to medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral hypothalamus (LH). While cocaine withdrawal increases glutamate release from LHb onto VTA-mPFC projectors, it reduces presynaptic release onto VTA-NAc projectors, leaving LHb synapses onto VTA-to-LH unaffected. Altogether, cocaine withdrawal promotes distinct adaptations at identified LHb-to-VTA circuits, which provide a framework for understanding the circuit basis of the negative states emerging during abstinence of drug intake.
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spelling pubmed-80442012021-04-15 Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal Clerke, Joseph Preston-Ferrer, Patricia Zouridis, Ioannis S. Tissot, Audrey Batti, Laura Voigt, Fabian F. Pagès, Stephane Burgalossi, Andrea Mameli, Manuel Front Synaptic Neurosci Neuroscience Projections from the lateral habenula (LHb) control ventral tegmental area (VTA) neuronal populations’ activity and both nuclei shape the pathological behaviors emerging during cocaine withdrawal. However, it is unknown whether cocaine withdrawal modulates LHb neurotransmission onto subsets of VTA neurons that are part of distinct neuronal circuits. Here we show that, in mice, cocaine withdrawal, drives discrete and opposing synaptic adaptations at LHb inputs onto VTA neurons defined by their output synaptic connectivity. LHb axons innervate the medial aspect of VTA, release glutamate and synapse on to dopamine and non-dopamine neuronal populations. VTA neurons receiving LHb inputs project their axons to medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral hypothalamus (LH). While cocaine withdrawal increases glutamate release from LHb onto VTA-mPFC projectors, it reduces presynaptic release onto VTA-NAc projectors, leaving LHb synapses onto VTA-to-LH unaffected. Altogether, cocaine withdrawal promotes distinct adaptations at identified LHb-to-VTA circuits, which provide a framework for understanding the circuit basis of the negative states emerging during abstinence of drug intake. Frontiers Media S.A. 2021-03-31 /pmc/articles/PMC8044201/ /pubmed/33867967 http://dx.doi.org/10.3389/fnsyn.2021.643138 Text en Copyright © 2021 Clerke, Preston-Ferrer, Zouridis, Tissot, Batti, Voigt, Pagès, Burgalossi and Mameli. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Clerke, Joseph
Preston-Ferrer, Patricia
Zouridis, Ioannis S.
Tissot, Audrey
Batti, Laura
Voigt, Fabian F.
Pagès, Stephane
Burgalossi, Andrea
Mameli, Manuel
Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title_full Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title_fullStr Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title_full_unstemmed Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title_short Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal
title_sort output-specific adaptation of habenula-midbrain excitatory synapses during cocaine withdrawal
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044201/
https://www.ncbi.nlm.nih.gov/pubmed/33867967
http://dx.doi.org/10.3389/fnsyn.2021.643138
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