Ensemble Dynamics of Cortical Feedback to the Thalamus

描述(申请人提供)：视觉处理中最引人注目和最悬而未决的问题之一是大量皮质反馈的作用，这些反馈发生在视觉系统的许多部位。这种反馈的激活被认为是注意力等过程的基础。它也可以作为绑定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大脑皮层，而是丘脑。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后的数据从皮质的第6层广泛重新输入到丘脑感觉核(如外侧膝状体核)的较低处理水平。我们建议描述皮质丘脑神经元和它们的目标丘脑中继器之间的通信规则(例如，多大比例的细胞参与，什么活动模式促进这种通信？)；丘脑内由此产生的活动模式可能是如何在地形图上表达的(例如，反馈是否促进某些类型的活动在某些地形区而不是其他区域？)；这些模式中的差异是如何允许某些类型的信息进入皮质的关键(例如，丘脑神经元有两种放电机制：爆发性和紧张性，这两种模式是否会对丘脑皮质(TC)突触产生不同的影响？)。信息会选择性地影响众所周知的生理类型的神经元吗？(例如，开/关、类似X/Y和/或眼睛特定信息？)为了回答这些问题，多电极阵列将被用来记录丘脑整体及其与大脑皮层第六层正在进行的对话。我们将检验以下假设：(H1)第六层对LGN的反馈将在依赖视觉注册的LGN细胞群之间产生关联；(H2)LGN细胞在某些放电条件和活动模式下将优先激活第六层神经元；以及(H3)脑干激活将增加LGN神经元对第六层反馈的相关放电。皮质丘脑相互作用的目的是一个经久不衰的谜，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。除了正常皮质丘脑处理的细节外，我们提出的研究将为了解癫痫、慢性疼痛和帕金森病等中枢神经系统疾病中异常的丘脑网络状态提供基础。相关性：来自外周感觉系统的信息在丘脑和皮质的上升阶段被处理。大脑皮层向大脑较低的处理水平发送大量的投射，但这种反馈的功能还很少被理解。该项目建议详细研究皮层如何指示丘脑根据刺激或空间物体排列的特定时间段，允许某些类型的信息进入更高的处理阶段。通过同时从两个区域的大量脑细胞进行记录，我们将发现这两个区域用来交流的规则。它们被一些大脑紊乱所困扰，因此我们将学习的关于基本沟通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.