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.
