Basal ganglia modulation of trigeminal intralaminar nuclei thalamic activity

描述（由申请人提供）：由基底神经节损伤引起的运动症状和潜在的神经病理学，如帕金森病（PD），已被广泛描述。然而，基底神经节在躯体感觉功能中的作用，包括疼痛和伤害感觉，在很大程度上被忽视了。提出使用电物理方法探索基底神经节如何调节丘脑层内核中的伤害性神经元对持续三叉神经伤害性刺激的反应。我们的长期目标是了解基底神经节如何调节伤害性信息。黑质纹状体途径的多巴胺能变性有望增强丘脑神经元对持续伤害性三叉神经刺激的反应。第一个具体目的是通过测试电刺激丘脑尾状壳核（CPu）对丘脑层内核中伤害性神经元的反应性的影响，分析丘脑尾状壳核（CPu）与层内核之间的连通性。通过电刺激激活中央处理器有望改变伤害性丘脑神经元对面部有害化学和机械刺激的放电频率。这些电生理实验也将允许功能表征，伤害性丘脑纹状体途径。这种丘脑纹状体通路以前没有被描述过。第二个具体目的是测试多巴胺耗竭对丘脑层内核三叉神经痛觉神经元反应性的影响，并研究多巴胺耗竭如何影响疼痛行为。单侧向中央处理器注射6-羟多巴胺以破坏含多巴胺的神经元，有望改变丘脑层内核中伤害性神经元的诱发放电频率，并增加伤害性行为反应。这些实验将为基底神经节在疼痛和伤害感觉中的作用提供新的见解，并将揭示新的多巴胺能疼痛调节系统。观察到PD患者的疼痛可能是由这种疼痛调节系统的损伤引起的。这些研究将有助于解释PD患者表现出的复杂感觉症状，并可能提出新的治疗策略来减轻这种疼痛。

DESCRIPTION (provided by applicant): The motor symptoms and underlying neuropathology resulting from damage to the basal ganglia such as that in Parkinson's disease (PD) have been described extensively. However, the basal ganglia role in somatosensory function, including that of pain and nociception, has been largely ignored. The proposed use of electrophysic-logical methods explores how the basal ganglia modulate the response of nociceptive neurons in the intralaminar nuclei of the thalamus to persistent trigeminal nociceptive stimuli. Our long range goal is to understand how the basal ganglia modulate nociceptive information. Dopaminergic degeneration of the nigrostriatal pathway is expected to enhance the response of thalamic neurons to persistent nociceptive trigeminal stimuli. The first specific aim is to analyze the connectivity between the caudate- putamen (CPu) and intralaminar nuclei of the thalamus by testing the effects of electrical CPu stimulation on the responsiveness of nociceptive neurons in the intralaminar nuclei of the thalamus. Activation of the CPu by electrical stimulation is expected to alter the discharge frequency of nociceptive thalamic neurons to noxious chemical and mechanical stimulation of the face. These electrophysiological experiments will also permit functional characterization,of a nociceptive thalamostriatal pathway. This thalamostriatal pathway has not been described previously. The second specific aim is to test the effects of dopamine depletion on the responsiveness of trigeminal nociceptive neurons in the intralaminar nuclei of the thalamus and investigate how dopamine depletions affects pain behavior. Unilateral injection of 6-hydroxydopamine into the CPu to destroy dopamine-containing neurons is expected to alter the evoked discharge frequency of nociceptive neurons in the intralaminar nuclei of the thalamus and increase nociceptive behavioral responses. These experiments will provide new insights about the role of the basal ganglia in pain and nociception and will shed light on a new dopaminergic pain modulatory system. It is possible that pain observed patients with PD is caused by an impairment of this pain modulatory system. These studies will help explain the complex sensory symptoms exhibited by patients with PD and may suggest new treatment strategies to alleviate such pain.