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Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications

Prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among glutamatergic principal neurons and GABAergic interneurons, as well as its long-range connections with other brain regions, have been...

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Detalles Bibliográficos
Autores principales: Yan, Zhen, Rein, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523584/
https://www.ncbi.nlm.nih.gov/pubmed/33875802
http://dx.doi.org/10.1038/s41380-021-01092-3
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author Yan, Zhen
Rein, Benjamin
author_facet Yan, Zhen
Rein, Benjamin
author_sort Yan, Zhen
collection PubMed
description Prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among glutamatergic principal neurons and GABAergic interneurons, as well as its long-range connections with other brain regions, have been functionally linked to specific behaviors, ranging from working memory to reward seeking. The efficacy of synaptic signaling in PFC network is profundedly influenced by monoaminergic inputs via the activation of dopamine, adrenergic or serotonin receptors. Stress hormones and neuropeptides also exert complex effects on the synaptic structure and function of PFC neurons. Dysregulation of PFC synaptic transmission is strongly linked to the social deficits, affective disturbance, and memory loss in brain disorders including autism, schizophrenia, depression and Alzheimer’s disease. Critical neural circuits, biological pathways, and molecular players that go awry in these mental illnesses have been revealed by integrated electrophysiological, optogenetic, biochemical, and transcriptomic studies of PFC. Novel epigenetic mechanism-based strategies are proposed as potential avenues of therapeutic intervention for PFC-involved diseases. This review provides an overview on PFC network organization and synaptic modulation, as well as the mechanisms linking PFC dysfunction to the pathophysiology of neurodevelopmental, neuropsychiatric and neurodegenerative diseases. Insights from the preclinical studies offer the potential for discovering new medical treatment of human patients with these brain disorders.
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spelling pubmed-85235842022-03-31 Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications Yan, Zhen Rein, Benjamin Mol Psychiatry Article Prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among glutamatergic principal neurons and GABAergic interneurons, as well as its long-range connections with other brain regions, have been functionally linked to specific behaviors, ranging from working memory to reward seeking. The efficacy of synaptic signaling in PFC network is profundedly influenced by monoaminergic inputs via the activation of dopamine, adrenergic or serotonin receptors. Stress hormones and neuropeptides also exert complex effects on the synaptic structure and function of PFC neurons. Dysregulation of PFC synaptic transmission is strongly linked to the social deficits, affective disturbance, and memory loss in brain disorders including autism, schizophrenia, depression and Alzheimer’s disease. Critical neural circuits, biological pathways, and molecular players that go awry in these mental illnesses have been revealed by integrated electrophysiological, optogenetic, biochemical, and transcriptomic studies of PFC. Novel epigenetic mechanism-based strategies are proposed as potential avenues of therapeutic intervention for PFC-involved diseases. This review provides an overview on PFC network organization and synaptic modulation, as well as the mechanisms linking PFC dysfunction to the pathophysiology of neurodevelopmental, neuropsychiatric and neurodegenerative diseases. Insights from the preclinical studies offer the potential for discovering new medical treatment of human patients with these brain disorders. 2022-01 2021-04-19 /pmc/articles/PMC8523584/ /pubmed/33875802 http://dx.doi.org/10.1038/s41380-021-01092-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Yan, Zhen
Rein, Benjamin
Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title_full Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title_fullStr Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title_full_unstemmed Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title_short Mechanisms of Synaptic Transmission Dysregulation in the Prefrontal Cortex: Pathophysiological Implications
title_sort mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523584/
https://www.ncbi.nlm.nih.gov/pubmed/33875802
http://dx.doi.org/10.1038/s41380-021-01092-3
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