Alternate pathways for the spread of excitation:Functional and behavioral studie

描述(由申请者提供)：理解感觉处理的一个基本步骤是识别其神经表现下的突触电路。破坏兴奋-抑制平衡的异常网络活动可能会产生严重的后果，导致癫痫、精神分裂症或帕金森氏症的发展。确定兴奋传播的机制将直接告知潜在的异常 在病理条件下出现。丘脑向皮质第四层(L4)的投射是感觉信息通过丘脑进入皮质的主要途径。信息被认为是沿着从L4到浅层L2/3到输出单元的一系列分层连接流动的 然而，丘脑神经元向皮质的几乎所有层发出稀疏的投射，特别是向L5/L6交界处。可能存在这样的机制，使得稀疏的投射在传播兴奋活动方面非常有效，而在电路的研究中往往忽略了这一点。这可能暗示了一种比之前认为的更复杂的感觉信息处理机制，通过这种机制，丘脑传递的信息通过直接平行的路径到达皮质输出神经元。利用光遗传学、电生理学和行为范式，我们建议证明直接丘脑皮质输入可以强烈地直接驱动L5输出神经元而不是L4活动，并确定直接和间接通路如何影响感觉行为。

DESCRIPTION (provided by applicant): An essential step in understanding sensory processing is to identify the synaptic circuitry underlying its neural representation. Aberrant network activity that disrupts excitation-inhibition balance can have severe consequences, contributing to the development of epilepsy, schizophrenia or Parkinson's disease. Identifying the mechanisms for the spread of excitation will directly inform about potential abnormalities that arise under pathological conditions. Thalamic projections to cortical layer 4 (L4) are the primary pathway by which sensory information enters the cortex via the thalamus. Information is thought to flow along a hierarchical series of connections from L4 to superficial L2/3, to the output cells in L5/6. However, thalamic neurons send sparse projections to virtually all layers of cortex, notably to the L5/L6 border. Mechanisms may exist that render sparse projections, often ignored in the study of circuits, highly effective in spreading excitatory activity. This would suggest a more complex mechanism of sensory information processing than previously thought, by which information relayed by thalamus reaches cortical output neurons via direct parallel pathways. Using optogenetics, electrophysiology, and behavioral paradigms, we propose to demonstrate that direct thalamocortical inputs can strongly, and directly drive L5 output neurons without L4 activity, and determine how the direct and indirect pathways affect sensory behavior.