Cortical VIP interneurons: behavioral recruitment, circuit mechanisms and subtypes

项目总结/摘要 皮质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体。在 在专门的局部计算中，皮层还从一个 各种远程神经调节中心。该提案调查了 这两种电路之间的关系。 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 其定义为血管活性肠多肽（VIP）的表达， 在四个不同的皮质区域解除抑制锥体细胞，从而定义了一个 典型皮层回路听觉皮层中的VIP中间神经元 被招募来响应强化信号（奖励和惩罚）， 很可能是由神经调节系统驱动的因此， 这一建议是为了确定VIP招聘的一般性， 强化信号和负责这种活动的电路机制。 首先，我们将评估VIP中间神经元募集的皮质范围的一般性， 使用复杂技术组合的神经元 确定和评价其活动。其次，我们将确定哪些输入 驱动VIP神经元的强化反应。我们将绘制所有公共区域 在大脑中，为皮层VIP神经元提供输入，重点是 胆碱能和多巴胺能神经调节系统，并决定 pathway（s）因果关系。最后，我们将确定 VIP神经元的亚型被募集和驱动。 这些目标的完成应该揭示VIP如何的基本原则- 受控的皮层微电路在皮层范围内起作用，并充当 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.