Layer 1 microcircuits mediating top-down modulation of sensory processing

项目2摘要 感觉知觉依赖于对来自感官的信号进行上下文调整的新皮质计算 具有内部信息(自上而下调制)。感官信息首先由初级感官传递 丘脑至新皮质第4层和5b/6层，并最终传递到锥体细胞的基树突。在……里面 相反，自上而下的信息来自许多不同的来源，包括皮质和皮质下 区域，主要针对上层的“联合”皮质层。在新皮质，GABA能中间神经元(INS) 是高度多样化的，在塑造电路活动的时空方面起着关键作用。此外， 新皮质GABA能中间神经元功能障碍与癫痫等疾病有关， 精神分裂症、焦虑症和自闭症谱系障碍。5HT3aR家族的INS是中国主要的IN人群 上层。项目2的目标是检验假设，即5HT3aR皮质胰岛素在 与上下文相关的感觉加工，主要集中在新皮质第一层(L1)。这一层是主要的目标 自上而下的输入。它不包含兴奋细胞，但由5HT3aR INS填充。在之前的资助期间 在这个PPG时期，我们在了解L1和L1的神经元组成方面取得了重大进展 产生了以这些神经元为靶点的实验试剂。基于这些进展，项目2将阐明 L1微电路调节自上而下的感觉加工。在目标1中，我们将使用成对的全细胞 切片记录、单突触狂犬病追踪和功能光遗传图谱以表征输入 和L1IN亚型在初级躯体感觉皮层的输出连通性，以阐明神经元 在L1中处理上下文信息的网络。在Aim 2中，将使用清醒小鼠的活体录音和 研究L1如何将初级感觉信息与语境整合的药物遗传学操作 依赖信息由两条不同的功能和临床重要途径传递，这两条途径不同 影响锥体细胞的活动。

Project 2 Summary Sensory perception depends on neocortical computations that contextually adjust signals from sensory organs with internal information (top-down modulation). Sensory information is first conveyed by the primary sensory thalamus to neocortical layers 4 and 5b/6 and is eventually relayed to the basal dendrites of pyramidal cells. In contrast, top-down information, which projects from many different sources, including cortical and subcortical regions, predominately targets upper ‘associative’ cortical layers. In the neocortex, GABAergic interneurons (INs) are highly diverse and have critical roles in sculpting the spatiotemporal aspects of circuit activity. Moreover, malfunction of neocortical GABAergic interneurons has been linked with diseases including epilepsy, schizophrenia, anxiety, and autism spectrum disorders. INs of the 5HT3aR family are the main IN population in the upper layers. The goal of Project 2 is to test the hypothesis that 5HT3aR cortical INs have important roles in context-dependent sensory processing and is focused on neocortical layer 1 (L1). This layer is the main target of top-down input. It contains no excitatory cells, but is populated by 5HT3aR INs. During the previous funding period of this PPG, we made significant advances in understanding the neuronal composition of L1 and generated experimental reagents to target these neurons. Based on these advances Project 2 will elucidate the L1 microcircuits mediating top-down modulation of sensory processing. In Aim 1 we will utilize paired whole-cell recordings in slices, monosynaptic rabies tracing, and functional optogenetic mapping to characterize the input and output connectivity of L1 IN subtypes in primary somatosensory cortex in order to elucidate the neuronal networks that process contextual information in L1. In Aim 2 will use in vivo recordings in awake mice and pharmacogenetic manipulations to investigate how L1 integrates primary sensory information with context dependent information conveyed by two distinct functionally and clinically important pathways that differentially impact the activity of pyramidal cells.