Distributed Neural Activity Patterns Underlying Practice-Based Learning

项目摘要/摘要 为了生存，动物必须学习感官暗示和运动动作之间的适当联系。 试错的过程。我们预计这种学习将加强 代表感觉提示的神经元和启动运动动作的神经元。强化的突触可能 是这些神经元群体之间的直接突触连接，或者通过这些中间系统 神经元，即“可塑性大脑回路”或“通路”。在许多不同的脑中观察到突触的可塑性 其机制也得到了较好的理解。然而，我们一直在努力确定哪一种 具体地说，塑料大脑回路是感觉线索-运动动作联系的基础，这种联系是通过 试错的过程。这在一定程度上是因为许多大脑区域经历了可塑性变化。 在学习的过程中，由于学习的经历招募了各种不同的认知过程，包括 感觉检测、运动控制、反馈、工作记忆和强化学习--认知过程 它们都涉及不同的大脑区域和分布的网络。在我的博士后期间，我开发了一种方法来 将这些认知功能分配给不同的大脑回路，以进行小鼠的反复试验学习。这个 该方法涉及一种创新的行为范式和光遗传工具，这些工具在空间和时间上 很精确。小鼠学会了将视觉皮层的光遗传激活(CUE)与前肢伸展到 抓起食物小球(运动动作)。作为我博士后工作的结果，我现在知道了大脑中的哪些神经元 对此提示进行编码，以及启动此马达动作所需的代码。因此，我现在有能力辨认 这条线索和这一动作之间的习得联系背后的可塑性大脑回路。在此，我建议 研究编码线索的神经元和启动运动所必需的神经元之间的大脑回路 行动，在活体内，而老鼠学习线索-行动联系。我会从线索开始研究神经活动的流动- 编码视觉皮质中的神经元到上丘中的神经元，这是启动 运动动作。在目标1中，我将确定视觉皮质在学习过程中线索活动的变化。在《目标2》中，我会 确定在学习过程中上丘的活动是如何变化的。在目标3中，我将确定是否 这条通路的输出足以触发学习后的运动动作。因此，这项工作直接与 大脑倡议的一个关键目标是“证明大脑活动和行为之间的因果联系。”我会学会的 在这项技术专家萨巴蒂尼博士的指导下，AIM 1进行了体内双光子成像。AIMS 2 和3将在使用体内电生理学的独立阶段进行，这是一项技术，我 有丰富的工作经验。这些实验将有助于确定从视觉皮质到上级的路径。 小丘存储习得的联想记忆的小丘。寻找习得的感觉线索-运动的神经基础 行动关联对于治疗特定有害关联至关重要，例如在创伤后应激障碍、强迫症、 自闭症和焦虑症，一般不会干扰感觉或运动行为。

PROJECT SUMMARY / ABSTRACT To survive, animals must learn appropriate associations between sensory cues and motor actions through a process of trial and error. We expect that this learning will strengthen the synaptic connections between neurons representing the sensory cue and neurons initiating the motor action. The strengthened synapses may be direct synaptic connections between these neuronal populations or via systems intermediate between these neurons, i.e., a “plastic brain circuit” or “pathway.” Synaptic plasticity has been observed in many different brain areas, and the mechanisms are moderately well understood. However, we have struggled to identify which plastic brain circuit underlies, specifically, the sensory cue-to-motor action association that is learned through the process of trial and error. This is due, in part, to the fact that many brain areas undergo plastic changes during learning, as the experience of learning recruits a variety of different cognitive processes, including sensory detection, motor control, feedback, working memory and reinforcement learning -- cognitive processes that all engage different brain areas and distributed networks. During my postdoc, I developed an approach to assign these cognitive functions to different brain circuits for a case of trial and error learning in mice. The approach involved an innovative behavior paradigm and optogenetic tools that are spatially and temporally precise. Mice learned to associate the optogenetic activation of visual cortex (cue) with a forelimb reach to grab a food pellet (motor action). As a result of my postdoc work, I now know which neurons in the brain encode this cue and which are required to initiate this motor action. Therefore I am now equipped to identify the plastic brain circuit underlying the learned association between this cue and this action. Here I propose to study the brain circuit between the cue-encoding neurons and the neurons necessary to initiate the motor action, in vivo while mice learn the cue-action association. I will study the flow of neural activity from the cue- encoding neurons in the visual cortex to the neurons in the superior colliculus that are necessary to initiate the motor action. In Aim 1, I will identify changes in the cued activity in visual cortex over learning. In Aim 2, I will determine how activity in the superior colliculus changes over learning. In Aim 3, I will determine whether the output of this pathway is sufficient to trigger the motor action after learning. Hence this work speaks directly to a key goal of the Brain Initiative, to “demonstrate causal links between brain activity and behavior.” I will learn in vivo two-photon imaging for Aim 1 under the guidance of Dr. Sabatini, an expert at this technique. Aims 2 and 3 will be conducted in the independent phase using in vivo electrophysiology, a technique with which I have extensive experience. These experiments will help to identify a pathway from visual cortex to superior colliculus that stores a learned, associative memory. Finding the neural basis of learned, sensory cue-motor action associations will be essential to treat specific harmful associations, such as occur in PTSD, OCD, autism and anxiety, without generally disrupting sensory or motor behavior.