Improving cognition by understanding and harnessing the plasticity of gamma-generating circuits in prefrontal cortex

项目摘要/摘要 我们最近发表了一项研究，使用遗传编码电压指示器来表明伽马频率 (具体地说，~40赫兹)左、右侧大脑中丘脑区小白蛋白(PV)中间神经元之间的同步化 在特定的认知任务中通常会增加。此外，破坏这种同步的具体原因是 足以产生类似于精神分裂症患者的认知缺陷。最后，我们发现， 使用光遗传操作瞬时增加或降低伽马同步性导致持久 伽马同步性和认知的变化。因此，伽马同步性是认知的关键调节因素 可以经历双向可塑性，从而纠正或诱导认知缺陷。该项目现在将使用 基因编码电压指示器、光遗传学、化学遗传学、切片电生理学和钙 成像，以确定产生治疗性增加的干预和细胞/突触机制 有害的伽马同步性降低，并确切地阐明伽马同步性的变化如何影响 前额叶电路的信息处理。这将使我们更好地理解伽马是如何 同步性有助于正常认知，并揭示在以下条件下恢复认知的特定目标 作为精神分裂症。

PROJECT SUMMARY / ABSTRACT We recently published a study that used genetic encoded voltage indicators to show that gamma-frequency (specifically ~40 Hz) synchronization between parvalbumin (PV) interneurons in the left and right mPFC normally increases during specific cognitive tasks. Furthermore, specifically disrupting this synchrony was sufficient to produce cognitive deficits similar to those observed in schizophrenia. Finally, we have found that transiently increasing or decreasing gamma synchrony using optogenetic manipulations leads to long-lasting changes in both gamma synchrony and cognition. Thus, gamma synchrony is a key mediator of cognition that can undergo bi-directional plasticity thereby correcting or inducing cognitive deficits. This project will now use genetically encoded voltage indicators, optogenetics, chemogenetics, slice electrophysiology and calcium imaging, to identify interventions and cellular/synaptic mechanisms that produce therapeutic increases and deleterious decreases in gamma synchrony, and elucidate exactly how changes in gamma synchrony affect information processing by prefrontal circuits. This will lead to a greater understanding of how gamma synchrony contributes to normal cognition, and reveal specific targets for restoring cognition in conditions such as schizophrenia.