Differential Excitation of Cortical Neurons by Somatosensory Inputs

描述（由申请人提供）：目的：本提案阐述了丘脑传入控制皮质神经元兴奋性的突触机制。它的重点是丘脑投射到啮齿动物的躯体感觉“桶”皮层，皮层输入的触觉信息起源于胡须。具体来说，我将试图确定丘脑皮层传入如何产生差异兴奋的中间神经元和主细胞，并表征受体亚型，调节从丘脑到皮层的传输。本研究将以小鼠丘脑皮层切片为模型系统，运用电生理、形态学和影像学技术来检测突触功能。背景：躯体感觉信息通过丘脑传入投射进入皮层。在啮齿类动物的初级躯体感觉皮层中，丘脑皮层传入传递来自胡须的信息。在这里，这些传入神经在抑制性中间神经元和兴奋性主细胞上形成突触。因此，丘脑皮质纤维在两种皮质细胞之间分配信息，设置皮质处理的初始阶段。丘脑皮质纤维的分歧，中间神经元和主细胞提供了基础，在躯体感觉皮层，这是至关重要的，强制执行的时间精度的皮层反应胡须刺激的双突触前馈抑制。丘脑皮层传入神经通过向中间神经元产生比主细胞更大的输入来支持这一重要的双突触回路，从而建立“故障安全”以确保前馈抑制。然而，尚不清楚是什么机制允许丘脑皮质纤维介导向中间神经元和主细胞的差异输入。目的1：探讨丘脑皮层传入神经对抑制性中间神经元的强输入机制。通过记录丘脑皮质切片中的神经元并刺激丘脑，我将确定是什么对从丘脑接收输入的抑制性中间神经元产生更强的输入。目标2：表征负责从丘脑到皮质的突触传递的受体亚型，并确定它们在塑造局部前馈抑制回路行为中的作用。公共卫生关系：通过确定使用丘脑皮层系统传输到皮层的功能特性，我希望能够深入了解控制丘脑受体层兴奋和抑制之间平衡的机制，以及有助于触觉刺激的皮层辨别。更深入地了解调节皮质兴奋性的因素可能有助于开发旨在预防皮质区癫痫发生的治疗方法。

DESCRIPTION (provided by applicant): PURPOSE: This proposal addresses the synaptic mechanisms by which thalamic afferents control the excitability of cortical neurons. It is focused on the thalamic projection to the rodent somatosensory "barrel" cortex, the cortical input of tactile information originating from the whiskers. Specifically, I will seek to determine how thalamocortical afferents produce differential excitation of interneurons and principal cells, and characterize the receptor subtypes that regulate transmission from the thalamus into the cortex. I will use the mouse thalamocortical slice as a model system, and electrophysiological, morphological and imaging techniques to assay synaptic function. BACKGROUND: Somatosensory information enters the cortex via afferent projections from the thalamus. In the primary somatosensory cortex of rodents, thalamocortical afferents carry information originating from the whiskers. Here, these afferents make synapses onto both inhibitory interneurons and excitatory principal cells. Thalamocortical fibers thus distribute information between two cortical cells types, setting the initial phase of cortical processing. The divergence of thalamocortical fibers onto interneurons and principal cells provides the basis for disynaptic feed-forward inhibition in the somatosensory cortex, which is critical for enforcing the temporal precision of cortical responses to whisker stimulation. Thalamocortical afferents support this vital disynaptic circuit by producing larger inputs onto interneurons than principal cells, thereby establishing a "fail-safe" to ensure feed-forward inhibition. It is not known, however, what mechanisms allow thalamocortical fibers to mediate differential input to interneurons and principal cells. AIM 1: Determine the mechanisms underlying the stronger input of thalamocortical afferents onto inhibitory interneurons. By recording from neurons in thalamocortical slices and stimulating the thalamus, I will determine what produces stronger inputs to inhibitory interneurons receiving input from the thalamus. AIM 2: Characterize the receptor subtypes responsible for synaptic transmission from the thalamus to the cortex, and determine their role in shaping the behavior of local feed-forward inhibitory circuits. PUBLIC HEALTH RELAVENCE: By determining the functional properties of transmission into the cortex using the thalamocortical system, I hope to gain insight into the mechanisms that control the balance between excitation and inhibition in thalamic recipient layers, and that contribute to the cortical discrimination of tactile stimuli. A deeper understanding of the factors that regulate cortical excitability may contribute to the development of therapies aimed at preventing epileptogenesis in cortical areas.