Cortical mechanisms of learned spatial-temporal sequence coding

描述（由申请人提供）：大脑持续处理信息流，这些信息流通过尖峰活动的时间序列在神经水平编码。从这种活动中，大脑能够提取与行为相关的数据，并形成外部世界的内部表征，进而产生行为输出。大脑还利用其内部状态来预测外部刺激将如何变化;这些预测在执行行为规划中起着关键作用。目前尚不清楚这种处理在大脑中是如何完成的。建立活动序列，可塑性和这些内部表征的神经编码之间的关系将极大地告知我们对正常大脑功能的理解，并且对于理解与精神障碍相关的认知缺陷是必要的。 由于动物不能自我报告它们的认知状态，因此很难利用动物模型来探索序列学习的高级神经机制。一般来说，新皮层是根据一个单一的共同计划组织起来的，该计划赋予了一个特征性的局部结构，并且有证据表明，大脑区域由于其特定的输入而获得功能分化。在这个框架中，视觉皮层之所以是“视觉的”，主要是因为它连接到视网膜，并且皮层的所有区域都能够解决类似的信息处理问题。这表明，在“高级”皮层区域中用于学习序列的基本机制也应该存在于“低级”区域中，并导致了初级感觉区域应该包含局部编码序列表征所需的机制的假设。一系列的实验验证了这一假设，这是可能的，在初级视觉皮层的时间和空间精度的视觉序列夹带。 本研究旨在充分描述和理解这种学习的机械性质及其对皮层处理的后果。所提出的实验的目的是测试的假设，即视觉序列的学习是由NMDAR介导的突触可塑性的神经元群体之间的分布在皮层层局部V1使用的电生理学观察，2-光子显微镜，药理学和光遗传学操作，和计算建模的组合编码。

DESCRIPTION (provided by applicant): The brain continually processes streams of information that are coded at the neural level by temporal sequences of spiking activity. From this activity, the brain is able to extract behaviorally relevant data and form internal representations of the external world used, in turn, to create behavioral output. The brain also uses its internal state to make predictions about how external stimuli will change; these predictions play a critical role in executive behavioral planning. It is not known how this processing is accomplished in the brain. Establishing the relationship between activity sequences, plasticity and the neural coding of these internal representations will greatly inform our understanding of normal brain function and is necessary to understand the cognitive deficits associated with mental disorders. Since animals cannot self-report their cognitive state it is ver difficult to explore the high-level neural mechanisms of sequence learning using animal models. Generally speaking, the neocortex is organized according to a single common plan that imparts a characteristic local architecture and there is evidence suggesting that brain regions acquire functional differentiation as a result of their specific inputs. In this framework, visual cortex i "visual" primarily because it connects to the retina and all regions of cortex are capable of solving similar information processing problems. This suggests that the same basic mechanisms used to learn sequences in "higher" cortical regions should exist within "lower" regions as well and leads to the hypothesis that primary sensory areas should contain the mechanisms necessary to locally encode sequence representations. A series of experiments testing this hypothesis demonstrate that it is possible to entrain visual sequences in primary visual cortex with both temporal and spatial precision. This research aims to fully characterize and understand the mechanistic nature of this learning and its consequences for cortical processing. The proposed experiments are designed to test the hypothesis that visual sequence learning is encoded by NMDAR mediated synaptic plasticity between populations of neurons spread across the cortical layers locally within V1 using a combination of electrophysiological observation, 2- photon microscopy, pharmacological and optogenetic manipulation, and computational modeling.