Apr 29, 2008

Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation

BMC Neuroscience
S Tanaka

Abstract

The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC). This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged. The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerabil...Continue Reading

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References

Mentioned in this Paper

In Silico
Presynaptic Terminals
Initial Segment of Axon
Amphetamine
Cortex Bone Disorders
Adrenal Cortex Diseases
Prefrontal Cortex
Extracellular
Schizophrenia
Neural Inhibition

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