Modulation of hippocampal gamma oscillations by dopamine in heterozygous Reeler mice In vitro

Wang, Lu and Zhao, Dandan and Wang, Mengmeng and Vreugdenhil, Martin and Lin, Juntang and Lu, Chengbiao (2020) Modulation of hippocampal gamma oscillations by dopamine in heterozygous Reeler mice In vitro. Frontiers in Cellular Neuroscience. ISSN 1662-5102

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The reelin haploinsufficient heterozygous reeler mouse (HRM), an animal model of schizophrenia, has altered mesolimbic dopaminergic pathways, shares similar neurochemical, and behavioral properties with the patients with schizophrenia. Dysfunctional neural circuitry with impaired gamma (γ) oscillation (30–80 Hz) has been implicated in abnormal cognition in patients with schizophrenia. However, the function of neural circuitry in terms of γ oscillation and its modulation by dopamine has not been reported in HRM. In this study, first, we recorded γ oscillations in CA3 from wide type (WT) mice and HRM hippocampal slices, and studied the effects of dopamine (DA) on γ oscillations. We found that there was no difference in γ power between WT mice and HRM and that dopamine increased γ power of WT mice but not HRM, suggesting that dopamine modulations of network oscillations in HRM are impaired. Second, we found that N-methyl-D-aspartate receptor (NMDAR) antagonist itself increased γ power and occluded DA-mediated enhancement of γ power in WT mice but partially restored DA modulation of γ oscillations in HRM. Third, inhibition of phosphoinositide 3-kinase (PI3K), a downstream molecule of NMDAR, increased γ power and blocked the effects of DA on γ oscillation in WT mice and had no significant effect on γ power but largely restored DA modulation of γ oscillations in HRM. Our results reveal that impaired DA function in HRM is associated with dysregulated NMDAR-PI3K signaling, a mechanism that may be relevant in the pathology of schizophrenia.

Item Type: Article
Identification Number:
Date: 11 February 2020
Subjects: A100 Pre-clinical Medicine
B200 Pharmacology, Toxicology and Pharmacy
Divisions: Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Martin Vreugdenhil
Date Deposited: 29 Jan 2020 12:57
Last Modified: 30 Sep 2020 14:21

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