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NMDA 受体拮抗作用对自由活动大鼠脑内同时记录的局部场电位和组织氧水平的影响。

The effect of NMDA-R antagonism on simultaneously acquired local field potentials and tissue oxygen levels in the brains of freely-moving rats.

机构信息

Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland; Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.

Department of Psychology, Maynooth University, Maynooth, Co. Kildare, Ireland.

出版信息

Neuropharmacology. 2017 Apr;116:343-350. doi: 10.1016/j.neuropharm.2017.01.006. Epub 2017 Jan 11.

Abstract

Non-competitive NMDA receptor antagonists are known to induce psychosis-like symptoms in rodents. Administration of such compounds cause behavioural effects such as memory impairment and hyperlocomotion. Additionally, drugs such as phencyclidine (PCP), ketamine and MK-801 all cause distinctive increases in striatal local field potential (LFP) in the high frequency oscillation (HFO) band in the power spectrum (140-180 Hz). Amperometric sensors provide a means to measure tissue oxygen (tO; a BOLD-like signal) in the brains of freely-moving rats while simultaneously acquiring LFP using the same electrode. Carbon paste electrodes were implanted into the striatum and hippocampus of male Wistar rats. Rats were administered with saline, ketamine (10 mg/kg), MK-801 (0.1 mg/kg) and PCP (2.5 mg/kg) and recordings were made at 1 kHz using three different potentials (-650 mV to measure tO; 0 mV and +700 mV as control conditions). NMDA receptor antagonism caused significant increases in tO in both the striatum and the hippocampus. Power spectrum analysis showed significant increases in HFO power in the striatum but not in the hippocampus. Conversely, there were significant decreases in delta and alpha power along with increases in theta and gamma power in the hippocampus that were absent in the striatum. This supports findings that LFP can be obtained from an amperometric sensor signal; allowing simultaneous acquisition of two translational biomarkers of neuronal activity (LFP and tO).

摘要

非竞争性 NMDA 受体拮抗剂已知可在啮齿动物中诱导出类似精神病的症状。此类化合物的给药会引起行为效应,如记忆障碍和过度活跃。此外,苯环利定(PCP)、氯胺酮和 MK-801 等药物都会导致纹状体局部场电位(LFP)在频谱(140-180 Hz)的高频振荡(HFO)带中出现明显增加。安培传感器提供了一种在自由移动的大鼠大脑中测量组织氧(tO;一种类似 BOLD 的信号)的方法,同时使用同一电极获取 LFP。碳糊电极被植入雄性 Wistar 大鼠的纹状体和海马体中。给大鼠注射生理盐水、氯胺酮(10 mg/kg)、MK-801(0.1 mg/kg)和 PCP(2.5 mg/kg),并使用三种不同的电位(-650 mV 测量 tO;0 mV 和+700 mV 作为对照条件)以 1 kHz 的频率进行记录。NMDA 受体拮抗作用导致纹状体和海马体中的 tO 显著增加。功率谱分析显示 HFO 功率在纹状体中显著增加,但在海马体中没有增加。相反,在海马体中,delta 和 alpha 功率显著降低,theta 和 gamma 功率增加,而在纹状体中则没有这种情况。这支持了从安培传感器信号中可以获得 LFP 的发现;允许同时获得两种神经元活动的转化生物标志物(LFP 和 tO)。

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