Journal Article

Neuregulin-1 Modulates Hippocampal Gamma Oscillations: Implications for Schizophrenia

André Fisahn, Jörg Neddens, Leqin Yan and Andrés Buonanno

in Cerebral Cortex

Volume 19, issue 3, pages 612-618
Published in print March 2009 | ISSN: 1047-3211
Published online July 2008 | e-ISSN: 1460-2199 | DOI: http://dx.doi.org/10.1093/cercor/bhn107
Neuregulin-1 Modulates Hippocampal Gamma Oscillations: Implications for Schizophrenia

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Alterations in gamma-frequency oscillations are implicated in psychiatric disorders, and polymorphisms in NRG-1 and ERBB4, genes encoding Neuregulin-1 (NRG-1) and one of its receptors, designated ErbB4, are associated with schizophrenia. Here we show that NRG-1 selectively increases the power of kainate-induced, but not carbachol-induced, gamma oscillations in acute hippocampal slices. NRG-1β is more effective than NRG-1α, a splice variant with lower affinity for ErbB receptors, and neither isoform affects the network activity without prior induction of gamma oscillations. NRG-1β dramatically increases gamma oscillation power in hippocampal slices from both rats (2062 ± 496%) and mice (710 ± 299%). These effects of NRG-1β are blocked by PD158780, a pan-specific antagonist of ErbB receptors, and are mediated specifically via ErbB4 receptors, because mice harboring a targeted mutation of ErbB4 do not respond to NRG-1. Moreover, we demonstrate that 50% of gamma-amino butyric acidergic parvalbumin (PV)–positive interneurons, which heavily contribute to the generation of gamma oscillations, express ErbB4 receptors. Importantly, both the number of PV-immunoreactive interneurons (−31%) and the power of kainate-induced gamma oscillations (−60%) are reduced in ErbB4 knockout mice. This study provides the first plausible link between NRG-1/ErbB4 signaling and rhythmic network activity that may be altered in persons with schizophrenia.

Keywords: ErbB4; hippocampus; interneuron; mouse; parvalbumin; rat

Journal Article.  4705 words.  Illustrated.

Subjects: Neuroscience

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