Role of GABAergic interneuron types in context and rule representation in the medial frontal cortex investigated with 1P-imaging in the freely moving mouse

前额叶皮质在认知参数的表征中起着关键作用，包括与任务相关的感觉线索、注意力、动作选择和任务规则。然而，GABA能抑制中间神经元(IN)类型如何有助于活动细胞组装中上下文和规则的表示的形成和稳定，目前还知之甚少。我们的目标是在小鼠大脑的认知中枢内侧前额叶皮质(MPFC)解决这个基本问题，原因如下：1.锥体细胞(PC)，代表所有皮质区域的大多数细胞，受到GABA能抑制素的严格控制。2.PFC内的快峰神经元(可能是GABA能INS)被描述为具有语境选择性活动，而规则尖峰细胞(可能是谷氨酸能PC)在规则表征中起着重要作用。3.小白蛋白(PV)和生长抑素(SOM)表达的Ins(PVIs，SOMI)在工作记忆和空间表征中发挥着不同的作用。4.INS从CA1PC的深层分区接受直接输入，CA1PC是一个高度活跃的位置编码群体。基于这一知识，我们的目标是检查PVI和SOMI在上下文和规则表示过程中如何影响小鼠mPFC中单个细胞和细胞组件的活动。我们将通过对自由活动的小鼠的前额叶神经元群体进行单光子钙成像，以及利用光遗传学工具操纵PVI和SOMI活动来解决这一基本问题。根据这些结果，我们旨在阐明mPFC中中间神经元进行上下文和规则表征的电路机制。因此，我们的主要目标是研究INS，特别是PVI/SOMI如何影响代表mPFC中的规则和上下文的单个PC和PC程序集的活动。本项目将对支持mPFC中高级表示的IN类型的作用提供新的见解。

The prefrontal cortex plays a key role in representations of cognitive parameters, including task relevant sensory cues, attention, action selection, and task rules. However, how GABAergic inhibitory interneuron (IN) types contribute to the formation and stabilization of the representation of contexts and rules in active cell assemblies is little understood. We aim to address this fundamental question in the mouse medial prefrontal cortex (mPFC), the cognitive hub of the brain, for the following reasons: 1. Pyramidal cells (PCs), which represent the majority of cells in all cortical areas, are tightly controlled by GABAergic inhibitory INs. 2. Fast-spiking neurons (putatively GABAergic INs) within the PFC have been described to show context-selective activity, while regular spiking cells (putatively glutamatergic PCs) play a major role in rule representation. 3. Parvalbumin (PV) and somatostatin (SOM)-expressing INs (PVIs, SOMIs) have been found to fulfil differential roles in working memory and spatial representations. 4. INs receive direct input from deep subdivisions of CA1 PCs, a highly active place coding population. Building on this knowledge, we aim to examine how PVIs and SOMIs influence the activity of single cells and cell assemblies in the mouse mPFC during context and rule representation. We will address this fundamental topic by applying single photon calcium imaging of prefrontal neuron populations in freely moving mice, and by manipulating PVI and SOMI activity with optogenetic tools. With these results we aim elucidate the circuit mechanisms underlying contextual and rule representations conducted by interneurons in the mPFC. Thus, our major goal is to examine how INs, particularly PVIs/SOMIs, influence the activity of individual PCs and PC assemblies representing rules and contexts in the mPFC. This project will provide new insights on the role of IN types supporting high-level representations in the mPFC.