Ensemble Dynamics of Cortical Feedback to the Thalamus

描述（由申请人提供）：视觉处理中最引人注目和未解决的问题之一是视觉系统中许多部位发生的大量皮质反馈的作用。这种反馈的激活被认为是注意力等过程的基础。它也可以作为结合问题的部分解决方案，该问题已被提出依赖于神经元集合中的相关放电。最早的皮质反馈根本不是发生在皮层，而是发生在丘脑。与大脑皮层的反馈系统类似，皮质丘脑反馈的特点是将处理过的数据从皮层第6层广泛地重新输入到丘脑感觉核（如外侧膝状核（LGN））的较低处理水平。我们建议表征皮质丘脑神经元与其目标丘脑中继之间的通信规则（例如，参与的细胞比例，以及促进这种通信的活动模式？）；由此产生的丘脑活动模式如何在地形上表达（例如，反馈是否促进某些地形区域的某些类型的活动，而不是其他区域？）；以及这些模式的差异在允许某些类型的信息进入皮层方面是如何至关重要的（例如，丘脑神经元有两种放电机制：爆发和强直，它们对丘脑皮质突触有不同的影响吗？）在已知的生理类型的神经元中，信息是否选择性地受到影响？（例如，ON/OFF, X/Y-like，和/或眼睛特定信息？）为了回答这些问题，将使用多电极阵列来记录丘脑整体及其与皮层第6层的持续对话。我们将测试以下假设：（H1）第6层对LGN的反馈将产生LGN细胞群之间的相关性，这些细胞群依赖于与峰值第6层神经元的视位寄存器；（H2）在一定的放电条件和活动模式下，LGN细胞会优先激活Layer 6神经元；（H3）脑干激活将增加LGN神经元对第6层反馈的相关放电。皮质丘脑相互作用的目的是一个持久的谜，但它的解决将产生反馈在神经系统中定义作用的基本细节。除了正常皮质丘脑加工的细节外，我们提出的研究将为理解癫痫、慢性疼痛和帕金森病等中枢神经系统疾病中丘脑网络的异常状态提供基础。相关性：来自外周感觉系统的信息在丘脑和皮层的上升阶段被处理。大脑皮层将大量的信息投射回大脑较低的处理层，但人们对这种反馈的功能知之甚少。该项目提出了详细的研究，即皮层如何指示丘脑，根据特定的刺激时间或空间中物体的排列，允许某些类型的信息进入更高的处理阶段。通过同时记录两个区域的大量脑细胞，我们将发现这些区域用来交流的规则。这些在许多大脑疾病中受到干扰，因此我们将学习的关于交流基本规则的信息对于理解这些异常的大脑状况至关重要。

DESCRIPTION (provided by applicant): One of the most compelling and unresolved issues of visual processing is the role of the massive cortical feedback that occurs in a number of sites in the visual system. Activation of this feedback is thought to underlie processes such as attention. It may also serve as a partial solution to the binding problem, which has been proposed to rely on correlated firing in ensembles of neurons. The earliest cortical feedback does not occur in cortex at all, but in the thalamus. Similar to feedback systems in the cerebral cortex, corticothalamic feedback is characterized by extensive reentry of processed data from Layer 6 of cortex to lower processing levels in sensory thalamic nuclei such as the lateral geniculate nucleus (LGN). We propose to characterize the rules of communication between corticothalamic neurons and their target thalamic relays (e.g., what proportion of cells engage, and what patterns of activity promote this communication?); how might the resulting activity patterns within the thalamus be expressed topographically (e.g., does feedback promote certain types of activity in certain topographic regions and not others?); and how are the differences in these patterns critical in allowing certain kinds of information access to cortex (e.g., thalamic neurons have two firing regimes: burst and tonic, will these have differing impact at thalamocortical (TC) synapses?). Is information selectively affected in well-known physiological types of neurons? (e.g., ON/OFF, X/Y-like, and/or eye specific information?) To answer these questions, multielectrode arrays will be used to record thalamic ensembles and their ongoing dialog with Layer 6 of cortex. We will test the following hypotheses: (H1) that Layer 6 feedback to the LGN will produce correlations among ensembles of LGN cells that depend upon visuotopic register with spiking Layer 6 neurons; (H2) that LGN cells will preferentially activate Layer 6 neurons under certain firing conditions and activity patterns; and (H3) that brainstem activation will increase correlated firing across LGN neurons in response to Layer 6 feedback. The purpose of corticothalamic interactions is an enduring mystery, but one whose resolution will yield fundamental details of the defining role of feedback in neural systems. In addition to the details of normal corticothalamic processing, our proposed studies will provide a foundation for understanding abnormal thalamic network states in CNS disorders such as epilepsy, chronic pain and Parkinson's disease. Relevance: Information from peripheral sensory systems is processed at ascending stages of the thalamus and cortex. The cortex sends a massive projection back to lower processing levels of the brain, but the function of this feedback is poorly understood. This project proposes the detailed examination of how the cortex may instruct the thalamus to allow certain types of information to proceed to higher processing stages based on specific timing of stimulation or arrangement of objects in space. By recording from large numbers of brain cells in both regions simultaneously, we will discover rules that the regions use to communicate. These are perturbed in a number of brain disorders, thus the information we will learn about the basic rules of communication is vital for the understanding of these abnormal brain conditions.