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

项目总结/摘要 我们最近发表了一项研究，该研究使用遗传编码电压指示器来显示伽马频率 （特别是~40 Hz）左右mPFC中小清蛋白（PV）中间神经元之间的同步 通常在特定的认知任务中增加。此外，专门破坏这种同步是 足以产生类似于精神分裂症中观察到的认知缺陷。最后，我们发现， 使用光遗传学操作瞬时增加或减少γ同步性导致持久的 伽马同步性和认知的变化因此，伽马同步性是认知的一个关键中介， 可以经历双向可塑性，从而纠正或诱导认知缺陷。该项目将使用 遗传编码电压指示器，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措施和细胞/突触机制， 有害的减少，在伽马同步，并阐明究竟如何在伽马同步的变化影响 前额叶回路的信息处理。这将使我们更好地理解伽玛 同步有助于正常的认知，并揭示了在这种情况下恢复认知的特定目标， 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.