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Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats
The medial septum (MS) differentially impacts midbrain dopamine (DA) neuron activity via the ventral hippocampus, a region implicated in DA-related disorders. However, whether MS regulation of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is disrupted in a developmental disru...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120917/ https://www.ncbi.nlm.nih.gov/pubmed/30177811 http://dx.doi.org/10.1038/s41537-018-0059-3 |
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author | Bortz, David M. Grace, Anthony A. |
author_facet | Bortz, David M. Grace, Anthony A. |
author_sort | Bortz, David M. |
collection | PubMed |
description | The medial septum (MS) differentially impacts midbrain dopamine (DA) neuron activity via the ventral hippocampus, a region implicated in DA-related disorders. However, whether MS regulation of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is disrupted in a developmental disruption model of schizophrenia is unknown. Male Sprague-Dawley rats were exposed at gestational day 17 to methylazoxymethanol (MAM) or saline. As adults, NMDA (0.75 µg/0.2 µL) was infused into the MS, and either DA neuron activity in the VTA and SNc (7–9 anesthetized rats per group) or amphetamine-induced hyperlocomotion (AIH, 11-13 rats per group) was measured. MS activation produced a 58% increase in the number of spontaneously active DA neurons in VTA and a 37% decrease in SNc in saline rats. However, MS activation produced opposite effects on DA population activity in MAM rats, decreasing VTA DA activity by 51% and increasing SNc DA activity by 47%. MS activation also increased AIH by 113% in MAM rats, opposite of what is seen in intact rats. The effect in behavioral output may be due to disrupted GABAergic regulation of SNc as bicuculline infusion into vSub, which selectively prevented the MS activation-induced decrease in SNc DA activity in intact rats, prevented the increase in AIH and SNc DA activity in MAM rats. These findings demonstrate that the regulation of midbrain DA neurons by the MS is disrupted in this well-validated animal model, suggesting that it could be a potential locus for pharmacological intervention in disorders such as schizophrenia. |
format | Online Article Text |
id | pubmed-6120917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61209172018-09-04 Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats Bortz, David M. Grace, Anthony A. NPJ Schizophr Article The medial septum (MS) differentially impacts midbrain dopamine (DA) neuron activity via the ventral hippocampus, a region implicated in DA-related disorders. However, whether MS regulation of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is disrupted in a developmental disruption model of schizophrenia is unknown. Male Sprague-Dawley rats were exposed at gestational day 17 to methylazoxymethanol (MAM) or saline. As adults, NMDA (0.75 µg/0.2 µL) was infused into the MS, and either DA neuron activity in the VTA and SNc (7–9 anesthetized rats per group) or amphetamine-induced hyperlocomotion (AIH, 11-13 rats per group) was measured. MS activation produced a 58% increase in the number of spontaneously active DA neurons in VTA and a 37% decrease in SNc in saline rats. However, MS activation produced opposite effects on DA population activity in MAM rats, decreasing VTA DA activity by 51% and increasing SNc DA activity by 47%. MS activation also increased AIH by 113% in MAM rats, opposite of what is seen in intact rats. The effect in behavioral output may be due to disrupted GABAergic regulation of SNc as bicuculline infusion into vSub, which selectively prevented the MS activation-induced decrease in SNc DA activity in intact rats, prevented the increase in AIH and SNc DA activity in MAM rats. These findings demonstrate that the regulation of midbrain DA neurons by the MS is disrupted in this well-validated animal model, suggesting that it could be a potential locus for pharmacological intervention in disorders such as schizophrenia. Nature Publishing Group UK 2018-09-03 /pmc/articles/PMC6120917/ /pubmed/30177811 http://dx.doi.org/10.1038/s41537-018-0059-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Bortz, David M. Grace, Anthony A. Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title | Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title_full | Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title_fullStr | Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title_full_unstemmed | Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title_short | Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats |
title_sort | medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in mam vs. normal rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120917/ https://www.ncbi.nlm.nih.gov/pubmed/30177811 http://dx.doi.org/10.1038/s41537-018-0059-3 |
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