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Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons
Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which in addition to DA, glutamate or GABA are also released. The mole...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409506/ https://www.ncbi.nlm.nih.gov/pubmed/37409563 http://dx.doi.org/10.7554/eLife.87902 |
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author | Ducrot, Charles de Carvalho, Gregory Delignat-Lavaud, Benoît Delmas, Constantin VL Halder, Priyabrata Giguère, Nicolas Pacelli, Consiglia Mukherjee, Sriparna Bourque, Marie-Josée Parent, Martin Chen, Lulu Y Trudeau, Louis-Eric |
author_facet | Ducrot, Charles de Carvalho, Gregory Delignat-Lavaud, Benoît Delmas, Constantin VL Halder, Priyabrata Giguère, Nicolas Pacelli, Consiglia Mukherjee, Sriparna Bourque, Marie-Josée Parent, Martin Chen, Lulu Y Trudeau, Louis-Eric |
author_sort | Ducrot, Charles |
collection | PubMed |
description | Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which in addition to DA, glutamate or GABA are also released. The molecular mechanisms regulating the connectivity of DA neurons and their neurochemical identity are unknown. An emerging literature suggests that neuroligins, trans-synaptic cell adhesion molecules, regulate both DA neuron connectivity and neurotransmission. However, the contribution of their major interaction partners, neurexins (Nrxns), is unexplored. Here, we tested the hypothesis that Nrxns regulate DA neuron neurotransmission. Mice with conditional deletion of all Nrxns in DA neurons (DAT::NrxnsKO) exhibited normal basic motor functions. However, they showed an impaired locomotor response to the psychostimulant amphetamine. In line with an alteration in DA neurotransmission, decreased levels of the membrane DA transporter (DAT) and increased levels of the vesicular monoamine transporter (VMAT2) were detected in the striatum of DAT::NrxnsKO mice, along with reduced activity-dependent DA release. Strikingly, electrophysiological recordings revealed an increase of GABA co-release from DA neuron axons in the striatum of these mice. Together, these findings suggest that Nrxns act as regulators of the functional connectivity of DA neurons. |
format | Online Article Text |
id | pubmed-10409506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-104095062023-08-09 Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons Ducrot, Charles de Carvalho, Gregory Delignat-Lavaud, Benoît Delmas, Constantin VL Halder, Priyabrata Giguère, Nicolas Pacelli, Consiglia Mukherjee, Sriparna Bourque, Marie-Josée Parent, Martin Chen, Lulu Y Trudeau, Louis-Eric eLife Neuroscience Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which in addition to DA, glutamate or GABA are also released. The molecular mechanisms regulating the connectivity of DA neurons and their neurochemical identity are unknown. An emerging literature suggests that neuroligins, trans-synaptic cell adhesion molecules, regulate both DA neuron connectivity and neurotransmission. However, the contribution of their major interaction partners, neurexins (Nrxns), is unexplored. Here, we tested the hypothesis that Nrxns regulate DA neuron neurotransmission. Mice with conditional deletion of all Nrxns in DA neurons (DAT::NrxnsKO) exhibited normal basic motor functions. However, they showed an impaired locomotor response to the psychostimulant amphetamine. In line with an alteration in DA neurotransmission, decreased levels of the membrane DA transporter (DAT) and increased levels of the vesicular monoamine transporter (VMAT2) were detected in the striatum of DAT::NrxnsKO mice, along with reduced activity-dependent DA release. Strikingly, electrophysiological recordings revealed an increase of GABA co-release from DA neuron axons in the striatum of these mice. Together, these findings suggest that Nrxns act as regulators of the functional connectivity of DA neurons. eLife Sciences Publications, Ltd 2023-07-06 /pmc/articles/PMC10409506/ /pubmed/37409563 http://dx.doi.org/10.7554/eLife.87902 Text en © 2023, Ducrot et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Ducrot, Charles de Carvalho, Gregory Delignat-Lavaud, Benoît Delmas, Constantin VL Halder, Priyabrata Giguère, Nicolas Pacelli, Consiglia Mukherjee, Sriparna Bourque, Marie-Josée Parent, Martin Chen, Lulu Y Trudeau, Louis-Eric Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title | Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title_full | Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title_fullStr | Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title_full_unstemmed | Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title_short | Conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
title_sort | conditional deletion of neurexins dysregulates neurotransmission from dopamine neurons |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409506/ https://www.ncbi.nlm.nih.gov/pubmed/37409563 http://dx.doi.org/10.7554/eLife.87902 |
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