Layer 4 circuits and sensory processing

摘要 新皮层通过结合来自不同大脑的信息， 感觉方式，并将其与内部产生的信息，如记忆， 预期此外，皮层的处理和感知是通过以下动作来调整的： 在特定的行为状态下，如唤醒和注意力，新皮层中释放的神经调节剂。 在大多数感觉系统中，感觉信息通过来自感觉神经元的投射进入皮层。 丘脑，主要针对层4（L4）。因此，丘脑皮质反应的转换发生在 L4启动感觉信息的皮层处理，产生一种感觉感受器， 动物的行为需求。然而，我们对这一问题的认识仍然不够全面。 在行为过程中发生在L4中的感觉输入的转换以及介导这些转换的回路 转变这些信息对于理解感觉加工的机制是至关重要的， 对于治疗由感官知觉改变引起的疾病的干预措施是必要的。皮层处理 是由兴奋性或主神经元（PN）组成的动态微电路介导的， 向其他区域和多种抑制性GABA能中间神经元（IN）发出信号，这些神经元塑造皮质 电路，对信号处理至关重要。然而，由于其多样性和代表性低， 记录行为过程中的IN活动并了解其功能一直是一个挑战。这个项目 使用创新的方法（视紫红质辅助修补），这有利于有效的针对性， 在任何皮层深度的特定细胞类型的体内记录，以推进我们对L4回路的理解。的 研究主要集中在L4体感皮层的两个主要IN群体，即快速尖峰 表达小清蛋白的篮状细胞（PV IN）和表达生长抑素的IN（SST IN）， 共占L4 INS的80-90%。切片实验导致假设， L4 SST INs是胆碱能影响的主要靶点，调节PV IN活性。L4 PV IN 产生丘脑皮层输入的前馈抑制（FFI），从而控制特征选择性， L4 PN。本申请将检验L4 SST IN调节PV IN介导的PN抑制的假设， SST细胞的胆碱能激活导致L4产生的PN的去抑制 有助于乙酰胆碱增强感觉检测的机制。为了研究抑制解除 假设，在目标1中，我们将研究L4 PV IN和PN在行为状态期间的活性变化， 这些SST IN通常会增加它们的活性，以及操纵SST IN活性的效果。在目标2中， 将使用依赖于胆碱能调节的感觉检测任务来研究L4 SST的作用 IN对触摸反应的活性，以及SST IN的毒蕈碱激活对触摸反应的贡献。 感觉信号和行为表现的胆碱能增强。

Abstract The neocortex generates a representation of the outside world by combining information from different sensory modalities and integrating this with internally generated information, such as memories and expectations. Furthermore, cortical processing and perception are contextually adjusted by the actions of neuromodulators released in the neocortex during specific behavioral states such as arousal and attention. In most sensory systems, sensory information enters the cortex through projections from the sensory thalamus that primarily target layer 4 (L4). Thus, the thalamocortical response transformations occurring in L4 start the cortical processing of sensory information that results in a sensory percept that is optimized for the behavioral needs of the animal. However, we still have an incomplete understanding of the transformations of sensory input that take place in L4 during behavior and the circuits mediating these transformations. This information is critical for a mechanistic understanding of sensory processing, which is necessary for interventions to treat diseases resulting from altered sensory perception. Cortical processing is mediated by dynamic microcircuits composed of excitatory or principal neurons (PNs), which transmit signals to other areas and a diverse array of inhibitory GABAergic interneurons (INs), which sculpt cortical circuits and are critical for signal processing. However, due to their diversity and low representation, recording IN activity during behavior and understanding their function has been challenging. This project uses an innovative approach (Channelrhodopsin-assisted patching), that facilitates the efficient targeted in vivo recording of specific cell types at any cortical depth, to advance our understanding of L4 circuits. The studies are focused on the two main IN populations in L4 of somatosensory cortex, the fast-spiking parvalbumin--expressing basket cells (PV INs) and the somatostatin-expressing INs (SST INs), which together account for 80-90% of L4 INs. Experiments in slices have led to the hypothesis that the function of L4 SST INs, which are major targets of cholinergic influence, is to regulate PV IN activity. L4 PV INs produce feedforward inhibition (FFI) of thalamocortical inputs and thereby control the feature selectivity of L4 PNs. This application will test the hypotheses that L4 SST INs regulate PV IN-mediated inhibition of PNs, and that the disinhibition of PNs produced in L4 as a result of the cholinergic activation of SST cells contributes to the mechanisms by which ACh enhances sensory detection. To investigate the disinhibition hypothesis, in Aim 1 we will study the changes in activity of L4 PV INs and PNs during behavioral states in which SST INs normally increase their activity and the effects of manipulating SST IN activity. In Aim 2, we will use a sensory detection task that depends on cholinergic modulation to investigate the role of L4 SST IN activity on touch responses, and the contribution of the muscarinic activation of SST INs to the cholinergic enhancement of sensory signals and behavioral performance.