Document Type

Journal Article

Publication Date

10-2014

Journal

PLoS ONE

Volume

Volume 9, Issue 10

Inclusive Pages

Article number e109303

DOI

10.1371/journal.pone.0109303

Keywords

Action Potentials--drug effects; Dizocilpine Maleate--adverse effects; Excitatory Amino Acid Antagonists--adverse effects; Interneurons--metabolism; Receptors, N-Methyl-D-Aspartate--antagonists & inhibitors; Schizophrenia--genetics

Abstract

The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI) is considered a primary contributor to the pathophysiology of schizophrenia (SZ), but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice were treated with the NMDA receptor antagonist, MK-801, during the first week of life. During adolescence, we detected reduced spike latency and increased GluN2B-mediated NMDA current in FSIs, which suggests transient disruption of NMDA signaling during neonatal development exerts lasting changes in the cellular and synaptic physiology of neocortical FSIs. Overall, we propose these physiological disturbances represent a general impairment to the physiological maturation of FSIs which may contribute to schizophrenia-like behaviors produced by this model.

Comments

Reproduced with permission of PLoS ONE.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

Download

Included in

Pediatrics Commons

Share

COinS