Thalamocortical Stimulation of Somotosensory Interneurons

我的研究的总体目标是了解传入的感觉信息对皮层抑制和兴奋回路的激活进行调制的机制。这个建议的中心假设是，突触前GABAB，腺苷，和代谢型谷氨酸受体调节丘脑皮层刺激皮层抑制。越来越清楚的是，皮层抑制回路在感觉加工和皮层重组中起着非常重要的作用。因此，了解这些抑制性皮层回路的激活是如何被调节的，将为我们提供重要的见解，了解感觉处理是如何被改变的。也许在未来，人们将有能力通过受体激动剂或拮抗剂来改变感觉处理，以帮助新技能的学习，事故或中风后的再学习，或治疗具有异常皮层重组的幻肢痛等疾病。然而，在进行任何此类干预之前， 需要更详细的信息类型和亚型的受体，调节激活抑制皮层回路通过传入的感觉信息。开始演讲;为了弥补我们知识上的不足，并扩大在该赠款的头三年中发现的初步观察结果，提出了以下目标。具体目的1：验证代谢型谷氨酸受体调节抑制性神经元的丘脑皮质兴奋的假设。具体目标2：检验内源性释放GABA、腺苷的假设。谷氨酸可调节抑制性神经元的丘脑皮质兴奋。具体目标3：验证突触前GABA An、腺苷A1和代谢型谷氨酸受体调节成年动物丘脑皮质刺激的假说。具体目标4：为了验证皮质内和丘脑皮质突触受GABAB、腺苷和代谢型谷氨酸受体不同调节的假设。详细的药理学知识， 调节丘脑激活皮层抑制回路的机制的生理学可以改善对中风或事故恢复者的治疗。

The overall goal of my research is to understand the mechanisms by which the activation of cortical inhibitory and excitatory circuits by incoming sensory information is modulated. The central hypothesis of this proposal is that presynaptic GABAB, adenosinc, and metabotropic glutamate receptors modulate thalamocortical stimulation of cortical inhibition. It is becoming increasingly clear that cortical inhibitory circuits play very important roles in sensory processing and cortical reorganization. Therefore, understanding how the activation of these inhibitory cortical circuits is regulated will provide important insights into how sensory processing can be altered pharmacologically. Perhaps in the future one would have the ability to alter sensory processing via receptor agonists or antagonists in order to assist in new skill learning, relearning after an accident or stroke, or treatment of conditions like phantom limb pain which have aberrant cortical reorganization. However, before any such interventions can be done we need more detailed information on the types and subtypes of receptors that regulate the activation of inhibitory cortical circuits via incoming sensory information. To begin to address; this deficit in our knowledge and extend the initial observations found during the first three years of this grant, the following aims are proposed. Specific Aim 1: To test the hypothesis that metabotropic glutamate receptors modulate thalamocortical excitation of inhibitory neurons. Specific Aim 2: To test the hypothesis that endogenously released GABA, adenosine. and glutamate can modulate thalamocortical excitation of inhibitory neurons. Specific Aim 3: To test the hypothesis that presynaptic GABAn, adenosine A1 and metabotropic glutamate receptors modulate thalamocortical stimulation in adult animals. Specific Aim 4: To test the hypothesis that intracortical and thalamocortical synapses are differentially reg,ulated by GABAB, adenosine and metabotropic glutamate receptors. Detailed knowledge of the pharmacology and physiology of the mechanisms which regulate the thalamic activation of cortical inhibitory circuits could improve treatments for people recovering from strokes or accidents.