Journal
CEREBRAL CORTEX
Volume 24, Issue 9, Pages 2522-2532Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bht109
Keywords
development; electrophysiology; frontal cortex; interneuron; NMDA receptor antagonist
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Funding
- Faculty of Pharmaceutical Sciences at University of Copenhagen
- H. Lundbeck A/S
- Danish Agency for Science, Technology and Innovation (Drug Research Academy grant) [08-342-191]
- Lundbeck Foundation [R155-2013-16337] Funding Source: researchfish
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A compromised gamma-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenylmethylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by delta-subunit-containing GABA(A) receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life.
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