Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.
Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.
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DOI：
10.1016/j.nbd.2022.105756
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发表时间：
2022-08
影响因子：
6.1
通讯作者：
Lee, Darrin J.
中科院分区：
文献类型：
--
作者：
Zepeda, Nancy C.;Crown, Lindsey M.;Medvidovic, Sasha;Choi, Wooseong;Sheth, Megha;Bergosh, Matthew;Gifford, Raymond;Folz, Caroline;Lam, Phillip;Lu, Gengxi;Featherstone, Robert;Liu, Charles Y.;Siegel, Steven J.;Lee, Darrin J.
精神分裂症的认知症状几乎没有治疗方法。导致谷氨酸N-甲基-d-天冬氨酸（NMDA）受体功能减退的药理学药物（如MK-801）模拟了许多这些症状并破坏了神经活动。最近的证据表明，内侧隔核（MSN）的脑深部刺激（DBS）可以调节内侧前额叶皮层（mPFC）和海马活动，并改善空间记忆。在这里，我们检查了急性MK-801给药对隔海马回路和行为内振荡活动的影响。我们还评估了MSN刺激改善MK-801给药后认知行为指标的潜力。59只Sprague道利雄性大鼠接受急性腹膜内（IP）生理盐水溶剂注射或MK-801（0.1 mg/kg）。在mPFC、MSN、丘脑和海马中分析Theta（5-12 Hz）、低伽马（30-50 Hz）和高频振荡（HFO）功率。大鼠在行为任务（新物体识别（NOR）、高架十字迷宫、巴恩斯迷宫（BM））期间经历MSN θ（7.7 Hz）、γ（100 Hz）或无刺激。注射MK-801导致振荡活动的频率特异性变化，降低θ，同时增加HFO功率。Theta刺激增强MK-801对高架十字迷宫的抗焦虑作用，但γ刺激不增强。虽然MK-801处理的大鼠在巴恩斯迷宫中表现出空间记忆缺陷，但那些也接受MSN θ刺激而不是γ刺激的大鼠更快地找到了逃避孔。这些结果表明，MK-801急性给药导致隔海马回路中的神经活动改变和空间记忆受损。此外，这些研究结果表明，MSN θ频率刺激改善特定的空间记忆缺陷，并可能是一种可能的治疗由NMDA功能减退引起的认知障碍。
Few treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory. Here, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration. 59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5–12 Hz), low gamma (30–50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)). Injection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner. These findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.
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影响因子：
3.5
作者：
Buzsáki, G
通讯作者：
Buzsáki, G
影响因子：
3.2
作者：
Lazarewicz, Maciej T.;Ehrlichman, Richard S.;Siegel, Steven J.
通讯作者：
Siegel, Steven J.
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
3.3
作者：
Kiss, T.;Feng, J.;Hajos, M.
通讯作者：
Hajos, M.
影响因子：
5.3
作者：
Jo, Yong Sang;Park, Eun Hye;Choi, June-Seek
通讯作者：
Choi, June-Seek