Epilepsy Development and Cognition Group, Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT, USA.
Epilepsy Development and Cognition Group, Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT, USA.
Neurobiol Dis. 2023 Mar;178:106021. doi: 10.1016/j.nbd.2023.106021. Epub 2023 Jan 28.
There is increasing human and animal evidence that brain oscillations play a critical role in the development of spatial cognition. In rat pups, disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition. Early-life seizures are associated with long-term deficits in spatial cognition and aberrant hippocampal oscillatory activity. Here we asked whether modulation of hippocampal rhythms following early-life seizures can reverse or improve hippocampal connectivity and spatial cognition. We used optogenetic stimulation of the medial septum to induce physiological 7 Hz theta oscillations in the hippocampus during the critical period of spatial cognition following early-life seizures. Optogenetic stimulation of the medial septum in control and rats subjected to early-life seizures resulted in precisely regulated frequency-matched hippocampal oscillations. Rat pups receiving active blue light stimulation performed better than the rats receiving inert yellow light in a test of spatial cognition. The improvement in spatial cognition in these rats was associated with a faster theta frequency and higher theta power, coherence and phase locking value in the hippocampus than rats with early-life seizures receiving inert yellow light. These findings indicate that following early life seizures, modification of hippocampal rhythms may be a potential novel therapeutic modality.
越来越多的人类和动物证据表明，脑振荡在空间认知的发展中起着关键作用。在记忆发育关键期通过光遗传学刺激破坏海马节律会损害空间认知。婴儿期癫痫与空间认知的长期缺陷和海马异常振荡活动有关。在这里，我们想知道早期癫痫发作后海马节律的调节是否可以逆转或改善海马连接和空间认知。我们在生命早期癫痫发作后空间认知的关键时期，使用光遗传学刺激中隔区来诱导海马体的生理 7 Hz theta 振荡。中隔区的光遗传学刺激在对照和早期癫痫发作的大鼠中导致精确调节的频率匹配的海马振荡。在空间认知测试中，接受主动蓝光刺激的大鼠表现优于接受惰性黄光刺激的大鼠。这些大鼠的空间认知能力的提高与海马体中更快的 theta 频率以及更高的 theta 功率、相干性和相位锁定值相关，而接受惰性黄光刺激的早期癫痫发作大鼠则没有这种相关性。这些发现表明，在生命早期癫痫发作后，海马节律的修饰可能是一种潜在的新的治疗方式。
