作者
Dechuan Sun, Mojtaba Kermani, Matt Hudson, Xin He, Ranjith Rajasekharan Unnithan, Chris French
发表日期
2020/5/26
期刊
bioRxiv
页码范围
2020.05. 26.116343
出版商
Cold Spring Harbor Laboratory
简介
Local field potentials (LFPs) recorded intracranially display a range of location specific oscillatory spectra which have been related to cognitive processes. Although the exact mechanisms producing LFPs are not completely understood, it is likely that voltage-gated ion channels which produce action potentials and patterned discharges play a significant role. It is also known that antipsychotic drugs (APDs) affect LFPs spectra and a direct inhibitory effect on voltage-gated potassium (Kv) channels has been reported. Additionally, Kv channels have been implicated in the pathophysiology of schizophrenia, a disorder for which APDs are primary therapies. In this study we sought to: i) better characterise the effects of two APDs on LFPs and connectivity measures and ii) examine the effects of potassium channel modulators on LFPs and potential overlap of effects with APDs. Intracranial electrodes were implanted in the hippocampus (HIP) and pre-frontal cortex (PFC) of C57BL/6 mice; power spectra, coherence and phase-amplitude cross frequency coupling were measured. Drugs tested were the APDs haloperidol and clozapine as well as voltage-gated potassium channel modulators (KVMs) 4-aminopyridine(4AP), tetraethylammonium (TEA), E-4031 and retigabine. All drugs and vehicle controls were administered intraperitoneally. Both APDs and KVMs significantly reduced gamma power with the exception of 4AP, which conversely increased slow-gamma power. Clozapine and retigabine additionally reduced coherence between HIP and PFC. Phase-amplitude coupling between theta and gamma oscillations in HIP was significantly reduced by the …
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