Development and function of 5HT3aR-expressing cortical GABAergic interneurons

大脑皮层的功能依赖于由两种类型的神经元组成的高度互连和动态的微电路，通过处理的各个阶段传播信号的GABA能兴奋性神经元和调节这种信息流并塑造皮层电路的GABA能中间神经元（IN）。皮质中的信号处理关键取决于这些中间神经元的活动。该计划项目的重点是对以前被低估的GABA能IN人群的特征进行描述。这些IN表达离子型5-羟色胺受体5 HT 3a，并且主要起源于尾神经节隆起（CGE）的发育过程中。初步研究表明，5-HT-3aR IN占躯体感觉皮层中总IN群体的约30%，并且它们集中在表层，在那里它们代表最大的IN群体。这表明它们在皮层的联合层中处理信息时很重要。5 HT 3aR INs是异质的，但它们通过离子型受体被5-羟色胺和乙酰胆碱均匀且有效地调节。该项目将研究皮质5 HT 3aR INs对大脑皮质发育和功能的作用。PPG将包括三个研究项目和两个核心（行政核心和分子和转基因核心），以支持三个项目的工作。项目I（Gordon Fishell）将阐明决定5 HT 3aR INs群体发展的机制。它将研究控制5 HT 3aR INs前体分化的遗传程序，它们在整个发育过程中的连接性以及它们在皮质成熟中的作用。项目II（Bernardo Rudy）将促进我们对5 HT 3aR INs在皮质功能中作用的理解。具体来说，它将测试的假设，它们是重要的上下文相关的感觉处理。它将研究5 HT 3aR INs的功能连接，使用光刺激表达通道视紫红质的胆碱能和多巴胺能轴突来研究它们通过这些皮层下输入的调节，并在体内进行双光子靶向记录来研究5 HT 3aR INs在不同行为状态下的活性及其对运动活动和感觉刺激的反应。项目III（由Wen-Biao Gan）将研究5-HT 3aR INs在第V层锥体神经元上形成的突触的位置、结构和可塑性，以及这些INs在调节锥体细胞在学习和记忆形成过程中的活性和结构动力学中的作用。

The functions of the cerebral cortex depend on highly interconnected and dynamic microcircuits composed of two types of neurons, glutamatergic excitatory neurons that propagate the signals through the various stages of processing and GABAergic interneurons (INs) that regulate this information flow and sculpt cortical circuits. Signal processing in the cortex depends critically on the activity of these interneurons. This Program Project is focused on the characterization of a population of GABAergic INs whose size and breadth have been previously underestimated. These INs express the ionotropic serotonin receptor 5HT3a and largely originate during development from the caudal ganglionic eminence (CGE). Preliminary studies show that 5HT3aR INs represent about 30% of the total IN population in somatosensory cortex, and that they are concentrated in superficial layers, where they represent the largest IN population. This suggests that they are important in the processing of information in the associative layers of cortex. 5HT3aR INs are heterogeneous, but they are uniformly and potently modulated by serotonin and acetylcholine via ionotropic receptors. The Program Project will investigate the roles of cortical 5HT3aR INs on the development and function of the cerebral cortex. The PPG will consist of three research projects and two cores (an Administrative Core and a Molecular and Transgenic Core) to support the work of the three projects. Project I (by Gordon Fishell), will elucidate the mechanisms that determine the development of the 5HT3aR INs population. It will investigate the genetic program that governs the differentiation of 5HT3aR INs precursors, their connectivity throughout development and the role of activity on their maturation in the cortex. Project II (by Bernardo Rudy) will advance our understanding of the role of 5HT3aR INs in cortical function. Specifically, it will test the hypothesis that they are important in context-dependent sensory processing. It will investigate the functional connectivity of 5HT3aR INs, use photostimulation of channelrhodopsin-expressing cholinergic and serotonergic axons to investigate their modulation by these subcortical inputs and two photon targeted recordings in vivo to investigate the activity of 5HT3aR INs during different behavioral states and their response to motor activity and sensory stimulation. Project III (by Wen-Biao Gan) will investigate the location, structure and plasticity of the synapses 5HT3aR INs make on layer V pyramidal neurons and the role of these INs in regulating the activity and structural dynamics of pyramidal cells during learning and memory formation.