Altered Cortical GABA Neurotransmission in Schizophrenia: Insights into Novel Therapeutic Strategies

Author(s): Ana D. Stan, David A. Lewis.

Journal Name:Current Pharmaceutical Biotechnology

Volume 13 , Issue 8 , 2012

Abstract:

Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain’s own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

Keywords: Chandelier neuron, basket neuron, parvalbumin, GABA-A receptor, prefrontal cortex, "axon terminals", "GABA synthesis", novel therapeutic strategies

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Article Details

VOLUME: 13
ISSUE: 8
Year: 2012
Page: [1557 - 1562]
Pages: 6
DOI: 10.2174/138920112800784925
Price: $58