Feature Finding Figure
Lower Gene Expression for KCNS3 Potassium Channel Subunit in Parvalbumin-Containing Neurons in the Prefrontal Cortex of Subjects with Schizophrenia

In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin (PV)-containing neurons. PV neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel a-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to PV neurons. This distinctive feature of PV neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical (PFC) γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, we investigated whether KCNS3 mRNA levels are altered in the PFC of schizophrenia subjects. KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects, and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a PV neuron-selective marker (figure; panels A-C), in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the PFC of antipsychotic-exposed monkeys. By ISH, KCNS3 mRNA levels were significantly 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower (figure; panels D-E). By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys. These findings reveal lower KCNS3 expression in PFC PV neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to PV neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.
Georgiev D, Arion D, Enwright JF, Kikuchi M, Minabe Y, Corradi J, Lewis DA, Hashimoto T. Lower Gene Expression for KCNS3 Potassium Channel Subunit in Parvalbumin-Containing Neurons in the Prefrontal Cortex of Subjects with Schizophrenia. Am J Psych, in press.

• Translational Neuroscience Program •
| Home |

David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
Phone: (412) 624-3894 - Fax: (412) 624-9910