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

破坏小白蛋白中间神经元产生的伽马振荡如何影响前额叶皮层规则转变的编码？

• 批准号: 10302949
• 负责人: Vikaas Singh Sohal
• 金额: $ 17.41万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302949
• 关键词: Affect; Alzheimer' s Disease; Association Learning; Behavior; Behavioral; Brain; Brain region; Code; Cognitive deficits; Communication; Computer Models; Corpus striatum structure; Cues; Development; Disease; Environment; Food; Frequencies; Heart; Impaired cognition; Impairment; Inherited; Interneurons; Laboratories; Learning; Left; Measurement; Measures; Medial; Mediating; Methods; Mus; Neurons; Odors; Organism; Output; Parvalbumins; Pattern; Periodicity; Phase; Play; Population Projection; Prefrontal Cortex; Process; Publishing; Rewards; Role; Schizophrenia; Signal Transduction; Specificity; Testing; Texture; Thalamic structure; base; behavioral outcome; cell type; cognitive function; cognitive task; combinatorial; disability; information processing; inhibitory neuron; network models; neural circuit; neural network; novel; optogenetics; parent grant; recruit; transmission process; unpublished works; voltage

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.

项目总结(母公司赠款) 在认知任务中，经常可以观察到大脑中电活动的节律性波动。在许多 在某些情况下，这些振荡是跨大脑区域同步的。伽马频率中的同步(~30- 100赫兹)范围被假设为促进大脑区域之间的交流，从而促进 认知功能。相反，伽马同步性的缺陷被假设为 精神分裂症、阿尔茨海默病和相关疾病的核心认知缺陷。然而，无论是 伽马同步性实际上有助于大脑功能，但仍存在很大争议。特定电路级 伽马同步的作用机制也不清楚。这项提议将利用两项优势 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来自 基因编码的电压指示器，以便在自由行为内量化伽马同步的变化 老鼠。其次，利用这种方法和光遗传学，我们发现了半球间的伽马同步性 在小鼠学习新线索时，前额叶皮质中的小白蛋白(PV)中间神经元起着关键作用。 奖励协会。我们假设：1)PV中间神经元的伽马频率活动在 投射到特定靶点的前额叶神经元；2)这些投射神经元的活动编码关键 与学习有关的信息；3)因此，伽马频率同步允许前额叶输出收敛 在具体的下游目标中建设性地促进关键任务相关信息的传递 通过一个延伸的前额叶网络来调节学习。这项提案将通过以下方式检验这些假设 伽马同步性是否从前额叶PV中间神经元传递到不同类别的 前额叶投射神经元，编码与任务相关的信息和/或到下游区域。我们会 然后构建一个计算模型来检验伽马同步的假设函数是一致的 根据我们的实验观察。这将揭示电路级机制，从而使伽马同步 以促进区域间交流和学习的方式通过神经网络传输。