NEURONAL CONNECTIONS AND RESPONSES IN CINGULATE CORTEX

扣带皮层中的神经元连接和反应

• 批准号: 3398782
• 负责人: Brent Alan Vogt
• 金额: $ 12.87万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3398782
• 关键词: acetylcholine; autoradiography; brain mapping; brain regulatory center; dendrites; dynorphins; electron microscopy; electrophysiology; fluorescence; human tissue; interneurons; laboratory rabbit; laboratory rat; ligands; motor neurons; muscarinic receptor; neural information processing; neuroanatomy; neuropeptide receptor; neurophysiology; opioid receptor; pain; periaqueductal gray matter; pyramidal cells; sectioning; sensorimotor system; silver impregnation; stimulus /response; thalamic nuclei; thalamocortical tract; tritium

Anterior cingulate cortex has been implicated in affective responses to noxious stimuli contains opioid synthesizing neurons and has high densities of mu and delta opioid receptors. It is not known which neuronal processes bind opioid receptor ligands. The present experiments will employ experimental localization techniques developed by the P.I. for localizing axonal and dendritic muscarinic acetylcholine receptor subtypes. For whole section analysis one of three types of lesions will be made in rat brain followed by assay of mu and delta-selective ligand binding in cryomicrotome sections, coverslip autoradiography and single grain counting in anterior cingulate cortex: 1) full depth or laminar ibotenic acid, 2) selective destruction of cortical projection neurons following injections of the immunotoxin OX7-ss- saporin into the caudate or periaqueductal gray nuclei or into posterior cingulate cortex, 3) deafferentation undercut lesions. A second localization approach will involve prelabeling of caudate, periaqueductal gray or cortical projection neurons with a stable, retrogradely transported fluorescent dye. Cortical neurons will then be enzymatically and mechanically dissociated and assayed for mu-selective binding of beta-funaltrexamine to prelabeled pyramidal neurons and unlabeled pyramidal and multipolar neurons. Another series of experiments will evaluate mu and delta sites in cortical sublaminae and thalamic subnuclei in cryomicrotome sections of rabbit and human brains. As a number of thalamic and cortical connections are likely involved in sensorimotor aspects of responses to noxious stimuli, multiple label connection studies are also proposed to analyze thalamocortical and corticocortical connections of rabbit cingulate cortex. Studies in thalamus will emphasize the lateral magnocellular nucleus because its connections have not been described and it is not known to exist in any other mammal. Studies at the cortical level will emphasize topographic relations among cingulate areas and among cingulate and visual areas. The main goals of these studies are to elucidate a direct means by which opiate and opioid compounds influence cortical neurons which project to autonomic and somatic motor centers, characterize the distribution of opioid receptors on the dendrites and somata of pyramidal projection neurons and multipolar interneurons and describe the connections of a virtually unknown nucleus in rabbit thalamus. Dissociated adult cortical neurons can be used in future studies to evaluate mechanisms of up and down regulation of opioid receptors as well as gating of ionic channels by opioid compounds.

前扣带皮层与情感有关 对有害刺激的反应包含阿片类合成神经元 并具有高密度的 mu 和 delta 阿片受体。 它不是 已知哪些神经元过程结合阿片受体配体。 这 目前的实验将采用实验定位 由 P.I. 开发的技术用于定位轴突和 树突状毒蕈碱乙酰胆碱受体亚型。 对于整体 将在大鼠中进行三种类型损伤之一的切片分析 随后对大脑进行 mu 和 delta 选择性配体结合分析 在冷冻切片机切片、盖玻片放射自显影和单 前扣带皮层颗粒计数：1) 全深度或 层状鹅膏蕈酸，2）选择性破坏皮质 注射免疫毒素 OX7-ss- 后的投射神经元 皂草素进入尾状核或导水管周围灰色核或进入 后扣带皮层，3）传入神经阻滞底切病变。 第二种定位方法将涉及尾状核的预标记， 导水管周围灰质或皮质投射神经元具有稳定的、 逆行运输荧光染料。 皮质神经元会 然后通过酶促和机械解离并进行测定 β-funaltrexamine 与预标记锥体的 mu 选择性结合 神经元和未标记的锥体神经元和多极神经元。 其他 系列实验将评估皮质中的 mu 和 delta 位点 冷冻切片机切片中的下层和丘脑亚核 兔子和人的大脑。 由于许多丘脑和皮质 连接可能涉及感觉运动方面 对有害刺激的反应，多标签连接研究 还建议分析丘脑皮质和皮质皮质 兔扣带皮层的连接。 对丘脑的研究将 强调外侧大细胞核，因为它的连接 尚未被描述，也不知道它存在于任何其他 哺乳动物。 皮质水平的研究将强调地形 扣带区之间以及扣带区与视觉之间的关系 地区。 这些研究的主要目标是阐明一种直接手段 哪些阿片和阿片类化合物影响皮质神经元 项目到自主和躯体运动中心，表征 阿片受体在树突和体细胞上的分布 锥体投射神经元和多极中间神经元 描述兔子中几乎未知的细胞核的连接 丘脑。 分离的成年皮质神经元可在未来使用 评估阿片类药物上调和下调机制的研究 受体以及阿片类化合物对离子通道的门控。