How does disrupting parvalbumin interneuron-generated gamma oscillations affect the encoding of rule shifts in the prefrontal cortex?

项目概要（赠款） 在认知任务期间，经常观察到大脑中电活动的节律性波动。在许多 在某些情况下，这些振荡在大脑区域之间是同步的。伽马频率（~30- 100 Hz）的范围已经被假设为促进大脑区域之间的通信，从而促进 认知功能。相反，伽马同步性的缺陷被假设有助于 认知缺陷是精神分裂症、阿尔茨海默病和相关疾病的核心。但无论 伽马同步对大脑功能的贡献仍然存在很大争议。具体电路级 伽马同步作用的机制也不清楚。该提案将利用两个 我们实验室的最新进展首先，我们开发了一种新的方法来分析信号， 基因编码的电压指示器，以便量化自由行为的 小鼠第二，使用这种方法和光遗传学，我们发现，大脑半球间的伽马同步 当小鼠学习新线索时，前额叶皮层中的小清蛋白（PV）中间神经元之间的联系起着关键作用- 奖励协会。我们假设：1）PV中间神经元的γ频率活动引起PV中间神经元的活动。 前额叶神经元投射到特定的目标; 2）这些投射神经元的活动编码了关键的 与学习相关的信息; 3）因此，伽马频率同步允许前额输出收敛 建设性地在具体的下游目标，促进关键任务相关信息的传输 通过扩展的前额叶网络来调节学习。本提案将通过以下方式检验这些假设： 研究伽马同步是否从前额叶PV中间神经元传递到各种类型的 编码任务相关信息的前额叶投射神经元和/或下游区域。我们将 然后构建一个计算模型来测试哪些假设的伽马同步函数是一致的 我们的实验观察。这将揭示伽马同步的电路级机制， 通过神经网络传输，以促进区域间的交流和学习。

PROJECT SUMMARY (PARENT GRANT) Rhythmic fluctuations of electrical activity in the brain are frequently observed during cognitive tasks. In many cases these oscillations are synchronized across brain regions. Synchronization in the gamma-frequency (~30- 100 Hz) range has been hypothesized to promote communication between brain regions, thereby facilitating cognitive functions. Conversely, deficits in gamma synchrony have been hypothesized to contribute to cognitive deficits at the heart of schizophrenia, Alzheimer’s disease, and related disorders. However, whether gamma synchrony actually contributes to brain function remains highly controversial. The specific circuit-level mechanisms through which gamma synchrony acts are also unclear. This proposal will take advantage of two recent developments in our laboratory. First, we have developed a new method for analyzing signals from genetically encoded voltage indicators in order to quantify changes in gamma synchrony within freely behaving mice. Second, using this method and optogenetics, we have found that interhemispheric gamma synchrony between parvalbumin (PV) interneurons in the prefrontal cortex plays a key role when mice learn new cue- reward associations. We hypothesize that: 1) gamma-frequency activity in PV interneurons entrains activity in prefrontal neurons which project to specific targets; 2) the activity of these projection neurons encodes key information related to learning; 3) thus, gamma-frequency synchronization allows prefrontal output to converge constructively in specific downstream targets, facilitating the transmission of critical task-relevant information across an extended prefrontal network that mediates learning. This proposal will test these hypotheses by studying whether gamma synchrony is transmitted from prefrontal PV interneurons to various classes of prefrontal projection neurons which encode task-relevant information and/or to downstream regions. We will then construct a computational model to test which hypothesized functions of gamma synchrony are consistent with our experimental observations. This will reveal circuit-level mechanisms whereby gamma synchrony is transmitted across neural networks in ways that can facilitate inter-regional communication and learning.