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A cholinergic hypothesis of the unconscious in affective disorders
The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulat...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837351/ https://www.ncbi.nlm.nih.gov/pubmed/24319409 http://dx.doi.org/10.3389/fnins.2013.00220 |
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author | Vakalopoulos, Costa |
author_facet | Vakalopoulos, Costa |
author_sort | Vakalopoulos, Costa |
collection | PubMed |
description | The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioral repertoires at the core of affective disorders and ADHD. Behavioral adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o) and its modulation of M1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signaling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial, recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behavior and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone. |
format | Online Article Text |
id | pubmed-3837351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-38373512013-12-06 A cholinergic hypothesis of the unconscious in affective disorders Vakalopoulos, Costa Front Neurosci Pharmacology The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioral repertoires at the core of affective disorders and ADHD. Behavioral adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o) and its modulation of M1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signaling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial, recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behavior and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone. Frontiers Media S.A. 2013-11-22 /pmc/articles/PMC3837351/ /pubmed/24319409 http://dx.doi.org/10.3389/fnins.2013.00220 Text en Copyright © 2013 Vakalopoulos. http://creativecommons.org/licenses/by/3.0/ 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) or licensor 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 | Pharmacology Vakalopoulos, Costa A cholinergic hypothesis of the unconscious in affective disorders |
title | A cholinergic hypothesis of the unconscious in affective disorders |
title_full | A cholinergic hypothesis of the unconscious in affective disorders |
title_fullStr | A cholinergic hypothesis of the unconscious in affective disorders |
title_full_unstemmed | A cholinergic hypothesis of the unconscious in affective disorders |
title_short | A cholinergic hypothesis of the unconscious in affective disorders |
title_sort | cholinergic hypothesis of the unconscious in affective disorders |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837351/ https://www.ncbi.nlm.nih.gov/pubmed/24319409 http://dx.doi.org/10.3389/fnins.2013.00220 |
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