Abstract
Background: The early phase of Alzheimer's disease (AD) involves the disruption of finely tuned neuronal circuitry in brain regions associated with learning and memory. This tuning is obtained from the delicate balance of excitatory and inhibitory inputs which regulate cortical network function. This homeostatic plasticity provides a dynamic basis for appropriate information transfer in the brain. Excitatory synaptic transmission is driven mainly by glutamatergic synapses whereas inhibitory synaptic transmission involves GABAergic and glycinergic signaling.
GABAergic cells, responsible for inhibitory transmission in adult brain, have recently become the subject of study in AD research. The discovery that GABAergic interneurons are targets of the amyloid-beta (Aβ) peptide suggest that deregulation of the excitatory/inhibitory balance contributes to changes in cortical regulation, possibly with consequences for the development of the pathology. Thus, understanding the molecular details involved in GABAergic alterations may provide insight into the pathogenesis of AD. Objective: Here, we review recent discoveries illustrating the concept of early alterations to the inhibitory circuits in AD and consider their functional implications for GABAergic components at membrane, cellular and microcircuit levels. Conclusion: We look at approaches that may lead to new hypotheses, animal models and therapeutic strategies based on GABAergic cells in AD with particular interest in microcircuits.Keywords: Amyloid-beta, GABAergic interneurons, long-range projecting neurons, neuronal microcircuits, synaptic transmission.
Current Alzheimer Research
Title:GABAergic Microcircuits in Alzheimer's Disease Models
Volume: 14 Issue: 1
Author(s): Vincent Villette and Patrick Dutar
Affiliation:
Keywords: Amyloid-beta, GABAergic interneurons, long-range projecting neurons, neuronal microcircuits, synaptic transmission.
Abstract: Background: The early phase of Alzheimer's disease (AD) involves the disruption of finely tuned neuronal circuitry in brain regions associated with learning and memory. This tuning is obtained from the delicate balance of excitatory and inhibitory inputs which regulate cortical network function. This homeostatic plasticity provides a dynamic basis for appropriate information transfer in the brain. Excitatory synaptic transmission is driven mainly by glutamatergic synapses whereas inhibitory synaptic transmission involves GABAergic and glycinergic signaling.
GABAergic cells, responsible for inhibitory transmission in adult brain, have recently become the subject of study in AD research. The discovery that GABAergic interneurons are targets of the amyloid-beta (Aβ) peptide suggest that deregulation of the excitatory/inhibitory balance contributes to changes in cortical regulation, possibly with consequences for the development of the pathology. Thus, understanding the molecular details involved in GABAergic alterations may provide insight into the pathogenesis of AD. Objective: Here, we review recent discoveries illustrating the concept of early alterations to the inhibitory circuits in AD and consider their functional implications for GABAergic components at membrane, cellular and microcircuit levels. Conclusion: We look at approaches that may lead to new hypotheses, animal models and therapeutic strategies based on GABAergic cells in AD with particular interest in microcircuits.Export Options
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Cite this article as:
Villette Vincent and Dutar Patrick, GABAergic Microcircuits in Alzheimer's Disease Models, Current Alzheimer Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567205013666160819125757
DOI https://dx.doi.org/10.2174/1567205013666160819125757 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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