Thalamocortical Stimulation of Somotosensory Interneurons

丘脑皮质刺激体感中间神经元

• 批准号: 7629039
• 负责人: James T. Porter
• 金额: $ 33.89万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7629039
• 关键词: Accidents; Address; Adenosine; Adult; Agonist; Chromosome Pairing; Class; Condition; Fiber; Future; GABA Receptor; Glutamates; Goals; Grant; Interneurons; Intervention; Knowledge; Learning; Metabotropic Glutamate Receptors; Mus; Neurons; Phantom Limb Pain; Pharmacology; Physiology; Play; Presynaptic Receptors; Research; Role; Sensory; Sensory Process; Stroke; Synapses; Testing; Thalamic structure; gamma-Aminobutyric Acid; improved; inhibitory neuron; insight; mature animal; neuromechanism; postsynaptic; presynaptic; prevent; receptor; skills

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.

我研究的总体目标是了解传入感觉信息调节皮质抑制和兴奋回路激活的机制。该提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质刺激皮质抑制。越来越清楚的是，皮质抑制回路在感觉处理和皮质重组中发挥着非常重要的作用。因此，了解如何调节这些抑制性皮层回路的激活将为了解如何从药理学上改变感觉处理提供重要的见解。也许在未来，人们将有能力通过受体激动剂或拮抗剂改变感觉处理，以协助新技能的学习、事故或中风后的重新学习，或治疗幻肢痛等皮质重组异常的病症。然而，在采取任何此类干预措施之前，我们 需要有关通过传入的感觉信息调节抑制性皮层回路激活的受体类型和亚型的更详细信息。开始解决；鉴于我们的知识不足，并扩展了在这笔赠款的前三年中发现的初步观察结果，提出了以下目标。具体目标 1：检验代谢型谷氨酸受体调节抑制性神经元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。谷氨酸可以调节丘脑皮质抑制性神经元的兴奋。具体目标 3：检验突触前 GABAn、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设。具体目标 4：检验皮质内和丘脑皮质突触受 GABAB、腺苷和代谢型谷氨酸受体差异调节的假设。详细的药理学知识和 调节丘脑皮质抑制回路激活机制的生理学可以改善中风或事故康复者的治疗。