Characterizing superior colliculus inputs to midbrain dopamine centers in cue learning

项目摘要 动物生活在复杂的、感官丰富的环境中。某些环境刺激（即线索）预测 有益的结果（即，这些都是生存的关键。为了妥善应对这些 预测刺激，我们必须能够区分这些线索从其他感官输入，并学习的价值， 他们在线索奖励学习中预测的奖励。了解这些背后的神经回路 过程是至关重要的，因为无序的感觉处理是几种精神疾病的标志， ADHD和物质使用障碍。腹侧被盖区（VTA）和腹侧黑质的多巴胺（DA）神经元 黑质背侧部（SNc）在线索奖励学习中至关重要，但目前尚不清楚这些区域如何整合 关于线索的感官信息，以驱动条件行为的独特方面。上级丘（SC）， 它接收来自视网膜的输入，已经显示出驱动DA神经元活动以响应视觉刺激， 破坏SC可以阻止DA活性和对视觉线索的条件反应。解剖和 SC投射到VTA/SNc在线索奖励学习中的功能尚不清楚。 为了解决这一知识差距，我将描述解剖和功能连接的特点， SC到VTA/SNc回路（目的1），并确定视觉提示过程中SC投射的贡献 学习（目标2）。为了研究这个回路的地形，我将追踪从SC到 VTA或SNc，并确定接收SC输入的神经元的投射目标。确定 SC输入到VTA和SNc的功能连接，我将通过光遗传学激发SC投射， 用在体纤维光度法记录腹侧被盖区和黑质核DA能神经元的活动。这些研究将测试 假设SC通过腹侧被盖区和黑质核的内侧到外侧连接驱动DA放电。我也会 测量和操纵SC投射活动（分别使用纤维光度学和光遗传学）， 视觉辨别学习任务，以检验SC向DA中脑的投射增加的假设。 条件行为与预测线索的联系这些研究将揭示SC如何与VTA进行沟通， SNc，对线索奖励学习的电路机制的基本见解。

PROJECT SUMMARY Animals exist in complex, sensory rich environments. Certain environmental stimuli (i.e. cues) predict beneficial outcomes (i.e., rewards) that are crucial for survival. In order to appropriately respond to these predictive stimuli, we must be able to discriminate these cues from other sensory input and learn the value of the rewards they predict, during cue-reward learning. Understanding the neural circuits underlying these processes is critical, as disordered sensory processing is a hallmark of several psychiatric diseases such as ADHD and substance use disorders. Dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) are critical in cue-reward learning, but it is not understood how these regions integrate sensory information about cues to drive unique aspects of conditioned behavior. The superior colliculus (SC), which receives input from the retina, has been shown to drive DA neuron activity in response to visual stimuli, and disrupting the SC can prevent DA activity and conditioned responding to visual cues. The anatomy and function of SC projections to the VTA/SNc in cue-reward learning is not known. To address this gap in knowledge, I will characterize the anatomical and functional connectivity of the SC to VTA/SNc circuit (Aim 1) and determine the contributions of SC projections during visual cue learning (Aim 2). To study the topography of this circuit, I will trace distinct pathways from the SC to either the VTA or SNc and determine the projection targets of the neurons that receive SC input. To determine the functional connectivity of SC inputs onto the VTA and SNc, I will excite SC projections via optogenetics while recording the activity of DA neurons in the VTA and SNc through in vivo fiber photometry. These studies will test the hypothesis that the SC drives DA firing via medial to lateral connections on the VTA and SNc. I will also measure and manipulate SC projection activity (using fiber photometry and optogenetics, respectively) during a visual discrimination learning task, to test the hypothesis that SC projections to the DA midbrain augment conditioned behaviors to predictive cues. These studies will reveal how the SC communicates with the VTA and SNc, for fundamental insights into the circuit mechanisms of cue-reward learning.