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.
Call for Papers in Thematic Issues
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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