Cortical VIP interneurons: behavioral recruitment, circuit mechanisms and subtypes

项目摘要/摘要 大脑皮层微电路的复杂结构被认为包括 执行基本计算的规范微电路的变种。在 在专门的局部计算中，CORACLE还从 各种远程神经调节中心。这项提案调查了 这两类电路之间的关系。 最近发现的一个皮层回路基序是由一类中间神经元控制的 由血管活性肠多肽(VIP)的表达来定义，VIP 抑制四个不同皮质区域的锥体细胞，从而定义 典型的皮质环路。听觉皮质中的这些VIP中间神经元是 为响应增援信号(奖励和惩罚)而招募，这 很可能是由神经调节系统驱动的。因此，我们的双重目标是 这项提案将通过以下方式确定贵宾招聘的一般性 增强信号和负责这一活动的电路机制。 首先，我们将通过以下方法评估VIP中间神经元募集的大脑皮层普适性 使用复杂技术组合的神经元增强剂 确定和评估他们的活动。第二，我们将确定哪些输入 驱动血管活性肠肽神经元的强化反应。我们将绘制所有公共区域的地图 为皮质VIP神经元提供输入的整个大脑，重点是 胆碱能和5-羟色胺能神经调节系统，并测定 路径(S)负有因果责任。最后，我们将确定不同之处 VIP神经元的亚型被招募和驱动。 完成这些目标应该揭示VIP如何- 受控皮质微电路在整个大脑皮层发挥作用，并作为 快速神经调节控制。

Project Summary/Abstract The complex architecture of cortical microcircuits is thought to comprise variations of canonical microcircuits that perform elemental computations. In the midst of specialized local computations, cortex also receives global input from a variety of long-range neuromodulatory centers. This proposal investigates the relationship between these two types of circuits. A recently identified cortical circuit motif is controlled by a class of interneurons defined by their expression of vasoactive intestinal polypeptide (VIP), which disinhibit pyramidal cells across four distinct cortical areas, thus defining a canonical cortical circuit. These VIP interneurons in the auditory cortex are recruited in response to reinforcement signals (reward and punishment), which are likely driven by neuromodulatory systems. Therefore the dual objectives of this proposal are to determine both the generality of VIP recruitment by reinforcement signals and the circuit mechanisms responsible for this activity. First we will evaluate the cortex-wide generality of VIP interneuron recruitment by reinforcers using a combination of sophisticated techniques for neuron identification and evaluation of their activity. Second, we will identify which inputs drive reinforcement responses in VIP neurons. We will map all common regions across the brain that provide inputs to cortical VIP neurons, with a focus on the cholinergic and serotonergic neuromodulatory systems and determine the pathway(s) causally responsible. Finally, we will determine how different subtypes of VIP neurons are recruited and driven. Completion of these aims should reveal fundamental principles of how the VIP- controlled cortical microcircuit functions cortex-wide and serves as a conduit for fast neuromodulatory control.