Lamina I and Homeostasis

层板 I 和稳态

• 批准号: 6624413
• 负责人: ARTHUR D CRAIG
• 金额: $ 34.9万
• 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/6624413
• 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.

从脊髓到达脑干的升序对于控制体内稳态（自主）功能的控制至关重要，例如对有害或热刺激的心血管和呼吸反应，这些反应挑战了人体稳定的生理状况。已有30多年的认可，即小直径（A-DELTA和C纤维）传入的输入在脑干中产生强大的SOMATO-SOMATO-SORATON-AUTONONIC反射，但是关于将这种活性携带到稳态脑系统整合位点的脊柱神经元的信息仍然很少。接收直接三角洲和C纤维的表面背角的层中神经元是脑干的脊柱输入的主要来源。我们在先前的工作中表明，层层I神经元将其投影到脑干的体内稳态区域。新的证据表明，Lamina I脊柱神经元是以前从未研究过的薄片I神经元的独特群体。该项目的目的是在解剖和生理上区分椎板I脊柱神经元。在解剖学研究中，我们（目标1）使用逆行标记来识别椎板I和其他将椎间性稳态部位投射到脑干中的特定稳态部位的椎体神经元，并验证将lamina I和其他将椎板神经元和其他投射到脑干中的特定稳态部位的脊柱神经元，并验证了lamina I I I Spinobulbar spinothalamic Neurons and Douptian-Douptian（使用双重型）。 在生理研究中，我们将（AIM 2）记录和表征单层椎骨I型脊柱神经元，使用抗胶质膜激活以及天然皮肤和深层的躯体刺激，并将其与脊柱丘脑神经元区分开。此外，我们将（AIM 3）刺激下丘脑和周期灰色，这是两个驱动交感神经血管收缩量输出的自主控制位点，以确定降低体内稳态控制是否会差异地调节脊柱纤维和脊柱瘤I神经元的活性。使用我们在猫的实验中精炼的方案（尽管如此，这些方案与灵长类动物具有基本的神经解剖学差异），这些实验将在猕猴中获得与人类生理学直接相关的数据。初步证据强烈表明，这些实验将证实中心假设，即椎板I脊柱神经元是不同的神经元群体。这些实验将首次与脑干中的稳态和自主神经自主神经整合机制携带小直径A-delta和C纤维传入输入的升高模态选择性脊柱神经元。基本知识将为解释对躯体生理变化的不良适应性稳态反应提供新的机会，包括诸如纤维肌痛之类的人类病理状况。