Role of novel VTA neurons in addiction-related behaviors

项目总结 腹侧被盖区(VTA)是驱动目标导向行为的神经回路的核心组成部分， 也是滥用药物调节行为的主要目标。尽管通常被认为是 多巴胺能核，大约一半的VTA神经元通过释放氨基酸神经递质来传递信号 GABA和谷氨酸。这些神经元也是药物滥用的目标，但研究要少得多。最近的证据 已经开始表明，像VTA DA神经元一样，VTA、GABA和谷氨酸中的活动 神经元可以深刻地塑造被激发的行为。此外，VTA神经元的亚群释放出更多 这三种循环递质中的一种，包括共同释放多巴胺和谷氨酸的神经元，或者 谷氨酸和GABA。该提案的目标是确定来自VTA的发射器共同释放如何有助于 行为强化背后的过程，以及共同释放的神经元如何在功能上整合到 调节动机行为的中脑边缘神经回路。我们将使用一系列的遗传方法 结合小鼠的行为、解剖和电生理测试，选择性地探索 分立VTA电路的连通性和功能。这一持续研究计划包括一个 详细计划定义新型VTA神经元的形态和功能，并提高我们的理解 固有的VTA异质性如何塑造与神经精神疾病相关的行为。

PROJECT SUMMARY The ventral tegmental area (VTA) is a core component of the neural circuitry that drives goal-directed behavior, and a primary target through which drugs of abuse modulate behavior. Although generally regarded as a dopaminergic nucleus, about half of VTA neurons signal through release of the amino acid neurotransmitters GABA and glutamate. These neurons are also targets of drugs of abuse but much less studied. Recent evidence from our lab and others has begun to show that, like VTA DA neurons, activity in VTA GABA and glutamate neurons can profoundly shape motivated behaviors. Furthermore, sub-populations of VTA neurons release more than one of these three recycling transmitters, including neurons that co-release dopamine and glutamate, or glutamate and GABA. The goals of this proposal are to identify how transmitter co-release from VTA contributes to the processes underlying behavioral reinforcement, and how co-releasing neurons functionally integrate into the mesolimbic neural circuits that regulate motivated behavior. We will use an array of genetic approaches in combination with behavioral, anatomical, and electrophysiological assays in mice to selectively probe the connectivity and function of discrete VTA circuits. Together this continuing research program comprises a thorough plan to define the form and function of novel classes of VTA neurons and enhance our understanding of how intrinsic VTA heterogeneity shapes behaviors relevant to neuropsychiatric disease.