Cortical mechanisms of learned spatial-temporal sequence coding

大脑不断地处理信息流，这些信息流是通过时间在神经层面上编码的 刺激性活动的序列。从这一活动中，大脑能够提取与行为相关的数据和形式 反过来，外部世界的内部表征被用来创造行为输出。大脑也使用它的 内部状态预测外部刺激将如何变化；这些预测在 执行行为规划。目前尚不清楚这一过程是如何在大脑中完成的。建立 活动顺序、可塑性与这些内部表征的神经编码之间的关系 将极大地启发我们对正常大脑功能的理解，并对理解认知能力是必要的 与精神障碍相关的缺陷。 由于动物不能自我报告自己的认知状态，因此很难探索高级神经 利用动物模型进行序列学习的机制。一般来说，新大脑皮层是有组织的 根据单一的共同计划，赋予了当地特色的建筑，并有证据 这表明，大脑区域由于其特定的输入而获得功能分化。在这 框架，视觉皮质之所以是“视觉的”，主要是因为它连接到视网膜，皮质的所有区域都 能够解决类似的信息处理问题。这表明，同样的基本机制 用来学习“较高”皮质区域的序列也应该存在于“较低”区域，并导致 假设主要感觉区应该包含局部编码序列所需的机制 申述。一系列测试这一假说的实验表明，它有可能将视觉 初级视皮层中的序列具有时间和空间精度。 本研究的目的是充分描述和理解这种学习及其机制的本质。 皮质处理的后果。拟议的实验旨在检验这样一个假设： 视觉序列学习由NMDAR介导的神经元群体之间的突触可塑性编码 使用电生理观察的组合，在V1内的局部皮质层扩散，2- 光子显微镜、药理学和光遗传操作以及计算模型。

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 very 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 is “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.