Perisomatic inhibition and cortical circuit dysfunction in schizophrenia

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Abstract

Deficits of cognitive control in schizophrenia are associated with altered gamma oscillations in the prefrontal cortex. Paralbumin basket interneurons, which innervate the perisomatic region of pyramidal neurons, appear to play a key role in generating cortical gamma oscillations. In the prefrontal cortex of subjects with schizophrenia, alterations are present in both pre- and post-synaptic markers of the strength of GABA inputs from parvalbumin basket neurons to pyramidal neurons. These alterations may contribute to the neural substrate for impaired gamma oscillations in schizophrenia.

Highlights

Cognitive deficits in schizophrenia are associated with altered gamma oscillations. ► Paralbumin basket neurons generate cortical gamma oscillations. ► In schizophrenia, inhibitory inputs from parvalbumin basket neurons are weaker. ► Altered inhibition may contribute to impaired gamma oscillations in schizophrenia.

Section snippets

Role of PV basket neurons in gamma oscillations

Cortical PV-containing GABA neurons consist of two major types: chandelier or axo-axonic cells which innervate the axon initial segment (AIS) of pyramidal neurons, and basket cells which innervate the cell body and proximal dendrites and spines of pyramidal neurons [20, 21, 22]. The location of these inputs onto the perisomatic membrane compartment indicates that both cell types are capable of activating relatively large GABAA receptor conductances near the site of action potential initiation

Alterations in prefrontal GABA neurons and gamma oscillations in schizophrenia

The findings reviewed above converge on the conclusion that perisomatic inputs from PV basket cells are the main source of GABAA receptor-mediated synchronization at gamma frequencies. This interpretation then raises the question of whether and how alterations in PV basket cells in the DLPFC of subjects with schizophrenia could provide the pathological basis for altered frontal lobe gamma oscillations. Because phasic excitation of PV neurons is thought to be required for gamma oscillations in

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

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