Lamina I and Homeostasis

层板 I 和稳态

• 批准号: 6474816
• 负责人: ARTHUR D CRAIG
• 金额: $ 34.5万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-19 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6474816
• 关键词: Macaca fascicularis; antidromic impulse; autonomic nervous system; autonomic reflex; brain stem; chemical stimulation; dorsal horn; electrostimulus; histology; homeostasis; hypothalamus; immunocytochemistry; injection /infusion; microelectrodes; monoclonal antibody; neurons; nociceptors; periaqueductal gray matter; somatic afferent nerve; thalamus; thermoreceptors

Ascending inputs to the brainstem from the spinal cord are critical for the control of homeostatic (pre-autonomic) functions, such as cardiovascular and respiratory responses to noxious or thermal stimuli that challenge the stable physiological condition of the body. It has been recognized for over 30 years that small-diameter (A-delta and C-fiber) afferent inputs generate powerful somato-autonomic reflexes in the brainstem, but there is still very little information available regarding the spinobulbar neurons that carry such activity to homeostatic brainstem integration sites. Neurons in lamina I of the superficial dorsal horn that receive direct - delta and C-fiber are the major source of spinal input to the brainstem. We have shown in prior work that lamina I neurons project to the homeostatic regions of the brainstem. New evidence suggests that lamina I spinobulbar neurons are unique population of lamina I neurons that has never been studied before. The goal of this project is to discriminate lamina I spinobulbar neurons anatomically and physiologically. In anatomic studies, we will (Aim 1) use retrograde labeling to identify lamina I and other spinal neurons that project to particular homeostatic sites in the brainstem and to verify that lamina I and other spinal neurons that project to particular homeostatic sites in the brainstem and to verify that lamina I spinobulbar an spinothalamic neurons are distinct (using double-labeling). In physiologic studies, we will (Aim 2) record and characterize single lamina I spinobulbar neurons, using antidromic activation and natural cutaneous and deep somatic stimulation, and differentiate them from spinothalamic neurons. In addition, we will (Aim 3) stimulate the anterior hypothalamus and the periacqueductal gray, two pre-autonomic control sites that drive sympathetic vasoconstrictor output, in order to determine whether descending homeostatic controls differentially modulate the activity of spinobulbar and spinothalamic lamina I neurons. Using protocols that we have refined in experiments in cats (which nonetheless have fundamental neuroanatomical differences from primates), these experiments will obtain data in macaque monkeys that will be directly relevant to human physiology. Preliminary evidence strongly indicates that these experiments will confirm the central hypotheses that lamina I spinobulbar neurons are a distinct population of neurons. These experiments will differentiate and characterize for the first time the ascending modality-selective spinal neurons that carry small- diameter A-delta and C-fiber afferent inputs to homeostatic and pre- autonomic integration mechanisms in the brain stem. The fundamental knowledge will provide new opportunities for explaining maladaptive homeostatic responses to somatic physiological changes, including such human pathological conditions as fibromyalgia.

从脊髓到脑干的上行输入对于控制稳态（前自主神经）功能至关重要，例如心血管和呼吸系统对挑战身体稳定生理状况的有害或热刺激的反应。 30多年来，人们已经认识到小直径（A-delta和C-纤维）传入输入会在脑干中产生强大的躯体自主反射，但是关于将这种活动传递给大脑的脊髓延髓神经元的信息仍然很少。稳态脑干整合位点。接受直接δ纤维和C纤维的浅表背角第一层神经元是脑干脊髓输入的主要来源。我们在之前的工作中已经证明，第一层神经元投射到脑干的稳态区域。新的证据表明，第一层脊髓延髓神经元是以前从未被研究过的独特的第一层神经元群体。该项目的目标是从解剖学和生理学上区分椎板 I 脊髓延髓神经元。在解剖学研究中，我们将（目标 1）使用逆行标记来识别投射到脑干中特定稳态位点的椎板 I 和其他脊髓神经元，并验证投射到脑干中特定稳态位点的椎板 I 和其他脊髓神经元和验证椎板 I 脊髓延髓和脊髓丘脑神经元是不同的（使用双标记）。 在生理学研究中，我们将（目标 2）使用逆向激活和自然皮肤和深层体细胞刺激来记录和表征单个椎板 I 脊髓延髓神经元，并将它们与脊髓丘脑神经元区分开来。此外，我们将（目标 3）刺激下丘脑前部和导水管周围灰质，这两个驱动交感血管收缩输出的前自主控制位点，以确定下降的稳态控制是否差异调节脊髓延髓和脊髓丘脑层 I 神经元的活动。使用我们在猫实验中完善的方案（尽管猫与灵长类动物在神经解剖学上存在根本差异），这些实验将获得与人类生理学直接相关的猕猴数据。初步证据有力地表明，这些实验将证实 I 层脊髓延髓神经元是一个独特的神经元群体的中心假设。这些实验将首次区分和表征上行模态选择性脊髓神经元，这些神经元携带小直径 A-delta 和 C 纤维传入输入到脑干中的稳态和前自主神经整合机制。基础知识将为解释对躯体生理变化（包括纤维肌痛等人类病理状况）的适应不良稳态反应提供新的机会。