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

通过移动小鼠的 1P 成像研究 GABA 能中间神经元类型在内侧额叶皮层上下文和规则表示中的作用

• 批准号: 513977628
• 负责人: Professorin Dr. Ilka Diester
• 金额: --
• 依托单位: Arbeitsgruppe Optophysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/513977628?language=en
• 关键词: Role; GABAergic; interneuron; types; context

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.

前额叶皮层在认知参数的表征中起着关键作用，这些认知参数包括任务相关的感觉线索、注意、动作选择和任务规则。然而，GABA能抑制性中间神经元（IN）类型如何有助于在活跃的细胞组装中形成和稳定的上下文和规则的表征却知之甚少。我们的目标是在小鼠内侧前额叶皮层（mPFC），大脑的认知中枢中解决这个基本问题，原因如下：1。锥体细胞（PC）是所有皮质区域中的主要细胞，它受到GABA能抑制性INS的严格控制。PFC内的快速发放神经元（pule-GABA能IN）被描述为显示上下文选择性活动，而规则发放细胞（pule-GABA能PC）在规则表征中起主要作用。3.小白蛋白（PV）和生长抑素（SOM）表达的INs（PVIs，SOMIs）已被发现在工作记忆和空间表征中发挥不同的作用。4. IN从CA 1 PC的深层细分中接收直接输入，CA 1 PC是一个高度活跃的位置编码群体。在此基础上，我们的目标是研究PVIs和SOMIs如何影响小鼠mPFC中的单个细胞和细胞组装体在上下文和规则表示过程中的活动。我们将通过对自由活动的小鼠前额叶神经元群体进行单光子钙成像，并通过用光遗传学工具操纵PVI和SOMI活性来解决这个基本问题。这些结果，我们的目的是阐明电路机制的背景和规则的表征进行中间神经元在mPFC。因此，我们的主要目标是研究如何的IN，特别是PVIs/SOMIs，影响活动的个人电脑和PC大会代表规则和上下文的mPFC。这个项目将提供新的见解的作用，在类型的支持高层次的代表性的mPFC。