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Medial septum differentially regulates dopamine neuron activity in the rat ventral tegmental area and substantia nigra via distinct pathways.

ABSTRACT: The medial septum (MS) impacts hippocampal activity and the hippocampus, in turn, regulates midbrain dopamine (DA) neuron activity. However, it remains to be determined how MS activation impacts midbrain DA activity. This question was addressed by infusing NMDA (0.75 µg/0.2 µL) into the medial septum of anesthetized male Sprague-Dawley rats and recording dopamine neuron activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). MS activation increased (71%) the number of spontaneously active DA neurons in the VTA, and decreased (40%) the number of active DA neurons in the SNc. Effects in both the VTA and SNc required the ventral subiculum, but were differentially dependent on cholinergic and GABAergic mechanisms within the vSub and rostral and caudal subregions of the ventral pallidum, respectively. MS activation also decreased amphetamine-induced locomotor behavior, which was dependent on GABAergic inputs to the hippocampus. These findings demonstrate that the MS differentially regulates meso-striatal DA transmission via distinct pathways.

SUBMITTER: Bortz DM

PROVIDER: S-EPMC6098086 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Medial septum differentially regulates dopamine neuron activity in the rat ventral tegmental area and substantia nigra via distinct pathways.

Bortz David M DM Grace Anthony A AA

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180327 10

The medial septum (MS) impacts hippocampal activity and the hippocampus, in turn, regulates midbrain dopamine (DA) neuron activity. However, it remains to be determined how MS activation impacts midbrain DA activity. This question was addressed by infusing NMDA (0.75 µg/0.2 µL) into the medial septum of anesthetized male Sprague-Dawley rats and recording dopamine neuron activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). MS activation increased (71%) the number ...[more]

PMID: 29654260

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Project description:Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner membrane of mitochondria. These enzymes create a proton gradient that is used to power the enzyme ATP synthase, producing ATP, which is crucial for the maintenance of cellular functioning. Anomalies in a single enzyme of the electron transport chain are sufficient to cause disruption of cellular metabolism. The last of these complexes is the cytochrome c oxidase (COX) enzyme, which is composed of thirteen different subunits. COX is a major site for oxidative phosphorylation, and anomalies in this enzyme are one of the most frequent causes of mitochondrial pathology. The objective of the present report was to assess if metabolic anomalies linked to COX dysfunction may contribute to substantia nigra/ventral tegmental area (SN/VTA) pathology in schizophrenia. We tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric controls. We also tested the protein expression of key subunits for the assembly and activity of the enzyme, and the effect of antipsychotic medication on subunit expression. COX activity was not significantly different between schizophrenia and non-psychiatric controls. However, we found significant decreases in the expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these decreases were observed in samples containing the entire rostro-caudal extent of the SN/VTA, while no significant differences were observed for samples containing only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with antipsychotic drugs did not show significant changes in COX subunit expression. These findings suggest that COX subunit expression may be compromised in specific sub-regions of the SN/VTA (i.e. rostral regions), which may lead to a faulty assembly of the enzyme and a greater vulnerability to metabolic insult.

Dataset Information

Medial septum differentially regulates dopamine neuron activity in the rat ventral tegmental area and substantia nigra via distinct pathways.

Publications

Medial septum differentially regulates dopamine neuron activity in the rat ventral tegmental area and substantia nigra via distinct pathways.

Similar Datasets

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