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14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway
While hippocampal hyperactivity is implicated in psychosis by both human and animal studies, whether it induces a hyperdopaminergic state and the underlying neural circuitry remains elusive. Previous studies established that region-specific inhibition of 14-3-3 proteins in the dorsal hippocampus CA1...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882652/ https://www.ncbi.nlm.nih.gov/pubmed/35237127 http://dx.doi.org/10.3389/fnmol.2022.817227 |
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author | Zhang, Jiajing Navarrete, Meaghan Wu, Yuying Zhou, Yi |
author_facet | Zhang, Jiajing Navarrete, Meaghan Wu, Yuying Zhou, Yi |
author_sort | Zhang, Jiajing |
collection | PubMed |
description | While hippocampal hyperactivity is implicated in psychosis by both human and animal studies, whether it induces a hyperdopaminergic state and the underlying neural circuitry remains elusive. Previous studies established that region-specific inhibition of 14-3-3 proteins in the dorsal hippocampus CA1 (dCA1) induces schizophrenia-like behaviors in mice, including a novelty-induced locomotor hyperactivity. In this study, we showed that 14-3-3 dysfunction in the dCA1 over-activates ventral tegmental area (VTA) dopaminergic neurons, and such over-activation is necessary for eliciting psychomotor behavior in mice. We demonstrated that such hippocampal dysregulation of the VTA during psychomotor behavior is dependent on an over-activation of the lateral septum (LS), given that inhibition of the LS attenuates over-activation of dopaminergic neurons and psychomotor behavior induced by 14-3-3 inhibition in the dCA1. Moreover, 14-3-3 inhibition-induced neuronal activations within the dCA1-LS-VTA pathway and psychomotor behavior can be reproduced by direct chemogenetic activation of LS-projecting dCA1 neurons. Collectively, these results suggest that 14-3-3 dysfunction in the dCA1 results in hippocampal hyperactivation which leads to psychomotor behavior via a dCA1-LS-VTA pathway. |
format | Online Article Text |
id | pubmed-8882652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88826522022-03-01 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway Zhang, Jiajing Navarrete, Meaghan Wu, Yuying Zhou, Yi Front Mol Neurosci Molecular Neuroscience While hippocampal hyperactivity is implicated in psychosis by both human and animal studies, whether it induces a hyperdopaminergic state and the underlying neural circuitry remains elusive. Previous studies established that region-specific inhibition of 14-3-3 proteins in the dorsal hippocampus CA1 (dCA1) induces schizophrenia-like behaviors in mice, including a novelty-induced locomotor hyperactivity. In this study, we showed that 14-3-3 dysfunction in the dCA1 over-activates ventral tegmental area (VTA) dopaminergic neurons, and such over-activation is necessary for eliciting psychomotor behavior in mice. We demonstrated that such hippocampal dysregulation of the VTA during psychomotor behavior is dependent on an over-activation of the lateral septum (LS), given that inhibition of the LS attenuates over-activation of dopaminergic neurons and psychomotor behavior induced by 14-3-3 inhibition in the dCA1. Moreover, 14-3-3 inhibition-induced neuronal activations within the dCA1-LS-VTA pathway and psychomotor behavior can be reproduced by direct chemogenetic activation of LS-projecting dCA1 neurons. Collectively, these results suggest that 14-3-3 dysfunction in the dCA1 results in hippocampal hyperactivation which leads to psychomotor behavior via a dCA1-LS-VTA pathway. Frontiers Media S.A. 2022-02-14 /pmc/articles/PMC8882652/ /pubmed/35237127 http://dx.doi.org/10.3389/fnmol.2022.817227 Text en Copyright © 2022 Zhang, Navarrete, Wu and Zhou. 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 | Molecular Neuroscience Zhang, Jiajing Navarrete, Meaghan Wu, Yuying Zhou, Yi 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title | 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title_full | 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title_fullStr | 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title_full_unstemmed | 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title_short | 14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway |
title_sort | 14-3-3 dysfunction in dorsal hippocampus ca1 (dca1) induces psychomotor behavior via a dca1-lateral septum-ventral tegmental area pathway |
topic | Molecular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882652/ https://www.ncbi.nlm.nih.gov/pubmed/35237127 http://dx.doi.org/10.3389/fnmol.2022.817227 |
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