CNS MEDIATION OF CONDITIONED BRADYCARDIA

条件性心动过缓的中枢神经系统调节

• 批准号: 3409844
• 负责人: PHILIP M MC CABE
• 金额: $ 9.49万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3409844
• 关键词: amygdala; bradycardia; brain mapping; central neural pathway /tract; conditioning; electrostimulus; heart rate; hypothalamus; laboratory rabbit; medial geniculate body; medulla oblongata; neuroanatomy; pons

The proposed behavioral experiments will explore the CNS pathways involved in the classical conditioning of heart rate responses in rabbits. Tone will be used as a conditioned stimulus (CS) and periorbital shock will serve as the unconditioned stimulus (US). In the rabbit, the conditioned heart rate response consists of heart rate slowing (bradycardia). The focus of the proposed project will be to describe the pathways mediating the CS and the conditioned response (CR), and to identify the structures in these pathways that are concerned with the discrimination between an associative CS (CS+) and a non-associative CS (CS-). Our strategy will involve: (a) using electrical stimulation techniques to elicit a cardiovascular response pattern from a given CNS site (e.g., primary bradycardia from sites along the CR pathway); (b) electrolytic lesions or administration of ibotenic acid along the pathway and assessment of the effects of the lesion or ibotenic acid administration on the differentially conditioned and/or unconditioned responses; (c) injection of horseradish peroxidase (HR), fluorescent tracers, or PHA-L into these CNS sites in order to trace anatomically anterograde and retrograde projections to and from the region; and (d) extracellular recording to determine if monosynaptic functional connections exist. Our research thus far has traced a bradycardia pathway originating in the central nucleus of the amygdala (ACE), which courses through the lateral hypothalamus, lateral zona incerta (LZI), and parabrachial nucleus of the pons, before terminating at the cells of origin of the vagus nerve in the medulla. Bilateral lesions of the LZI or ACE abolish the CR without influencing the UR, orienting response, or nictitating membrane conditioning, thereby suggesting that this pathway is the CR pathway. HRP injections into ACE produce cell body labeling in the medial geniculate nucleus (MGN), an auditory structure. Bilateral lesions of MGN abolish the ability to discriminate between a CS+ and CS- but do not affect the magnitude of the bradycardia CR, UR, or nictitating membrane differential conditioning. These data suggest that the CS pathway may be organized in a parallel fashion with rostral CS structures mediating discrimination, and more caudal CS structures mediating conditioned bradycardia responses. Knowledge of the pathways underlying learned cardiovascular adjustments could provide a biopsychological framework for studying possible learned aspects of cardiovascular pathophysiology and treatment.

提出的行为实验将探索中枢神经系统 心率经典条件涉及的途径 兔子的反应。 音调将用作条件刺激 （CS）和周围休克将充当无条件的刺激 （我们）。 在兔子中，条件心率反应包括 心率放缓（心动过缓）。 提议的重点 项目将描述介导CS和 条件响应（CR），并确定这些结构 与歧视的途径 联想CS（CS+）和非缔合CS（CS-）。 我们的策略 将涉及：（a）使用电刺激技术引起A 来自给定的中枢神经系统部位的心血管响应模式（例如， 沿CR通路的部位的主要心动过缓）； （b） 沿着电解病变或依靠尼酸的给药 病变或基因尼的途径和评估 在差异条件和/或 无条件的回应； （c）注射辣根过氧化物酶 （HR），荧光示踪剂或PHA-L到这些CNS位点的顺序 追踪解剖和逆行投影 并来自该地区； （d）确定细胞外记录 如果存在单突触功能连接。 因此，我们的研究 远方已追踪了一个源自中央的心动过缓途径 杏仁核的核（ACE），该核通过侧面的培训 下丘脑，外侧Zona incerta（LZI）和副核核 PON的），然后终止在迷走神的原点细胞之前 神经在髓质中。 Lzi或Ace的双侧病变废除 CR不影响UR，定向响应或 限制膜调节，从而表明这一点 路径是CR路径。 HRP注射到ACE农产品 内侧基因核（MGN）中的细胞体标记，一个 听觉结构。 MGN的双侧病变废除了能力 区分CS+和CS-但不会影响 心动过缓CR，UR或刺激膜的大小 差异条件。 这些数据表明CS途径 可以与Rostral CS结构平行组织 介导歧视和更多的尾部CS结构 介导条件心动过缓的反应。 了解 学习的心血管调整的途径可能 提供一个生物心理学框架来研究可能 学会了心血管病理生理学和治疗方面。