BARORECEPTOR TRANSMISSION VIA NTS GLUTAMATE RECEPTORS

通过 NTS 谷氨酸受体进行压力感受器传输

• 批准号: 2750523
• 负责人: JEANNE L SEAGARD
• 金额: $ 12.03万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750523
• 关键词: action potentials; afferent nerve; baroreceptors; blood pressure; carotid sinus; computational neuroscience; dogs; electrophysiology; glutamate receptor; neural transmission; neurophysiology; neurotransmitter antagonist; receptor expression; solitary tract nucleus; vascular smooth muscle nervous control

DESCRIPTION: (adapted from the abstract) Neural control of blood pressure (BP) involves both short-term, "beat-to-beat" regulation as well as longer, more tonic control of mean pressure. Two functional types of carotid sinus baroreceptors, which have been described previously, have been found to contribute differentially to these two aspects of BP control. Type I baroreceptors have been found to contribute more to dynamic control of BP, while Type II baroreceptors have been found to be major regulators of tonic BP. However, the site of elaboration of this differential baroreceptor control of BP is not known. Some differential control of BP may be due to the different patterns of afferent input from the two subtypes of baroreceptors. In addition, preliminary data indicates that afferent input from the baroreceptor subtypes may be directed to at least two different populations of neurons in the nucleus tractus solitarius (NTS), thought to be the site of the first synapse for baroreceptor afferent input in the CNS. Firing patterns of neurons from these two populations of NTS baroreceptor-modulated neurons are different. The first type of central neuron has an abrupt onset of discharge during pressure ramp stimulation of the carotid baroreceptors, which rapidly adapts in spite of continued baroreceptor activation. The second has ongoing discharge that is increased during carotid baroreceptor activation and does not show adaptation. Thus, in addition to the contributions of baroreceptor firing patterns to differential control of BP, selective activation of NTS baroreceptor-modulated neurons with different firing characteristics may also help regulate differential patterns of outflow of the autonomic nervous system. Studies have provided evidence that glutamate (GLU) is the primary neurotransmitter released by baroreceptor afferent fibers at the second order neurons in the NTS. However, the type of GLU receptors found on the second order neurons has not been established. Evidence exists for a role for NMDA, non-NMDA, metabotropic or combined types of receptors at putative baro-sensitive neurons in the NTS, although no functional role has been assigned for the receptors. The potential for differential distribution of glutamate receptors which initiate responses with different time courses and effects on the NTS neurons may contribute to the differential control of BP. Therefore, the overall aim of the present study is to examine static and dynamic characteristics of baroreceptor-modulated neurons in the NTS which may contribute to differential control of BP, with the intent of determining the contribution of GLU receptor subtype to the discharge of the NTS neurons activated by specific baroreceptor subtypes. The information obtained from these studies may provide insights into mechanisms of differential control of blood pressure under normal conditions and how alteration of this control may lead to pathologic states, including hypertension.

描述：（改编自抽象）血压的神经控制 （bp）涉及短期，“击败”法规以及更长的法规 对平均压力的更多补品控制。 两种功能性的颈动脉窦 以前已经描述的压力感受器已被发现 对BP控制的这两个方面有所不同。 类型I。 已发现压力感受器对BP的动态控制有更多的贡献 虽然已经发现II型压力感受器是补品的主要调节剂 bp。 但是，这种差异压力感受器的阐述 BP的控制尚不清楚。 BP的某些差异控制可能是由于 来自两个子类型的传入输入的不同模式 压力感受器。 此外，初步数据表明传入输入 从压力感受器亚型可以至少针对两个不同 神经元的群中的神经元种群，被认为是 成为中枢神经系统中压力感受器传入输入的第一个突触的位置。 来自这两个NT的神经元的射击模式 压力感受器调节的神经元不同。 中央的第一种类型 在压力坡道刺激期间，神经元突然发作 颈动脉压力受体，尽管持续迅速适应 压力感受器激活。 第二个有持续的排放量增加 在颈动脉压力受体激活期间，并未显示适应性。 因此， 除了压力感受器射击模式对 BP的差分控制，NTS的选择性激活 具有不同发射特征的压力感受器调节的神经元可能 还有助于调节自主神经流出流出的差异模式 系统。 研究提供了证据表明谷氨酸（GLU）是主要的 由Baroreceptor传入纤维发布的神经递质在第二张 在NTS中订购神经元。 但是，在 尚未确定二阶神经元。 存在角色的证据 对于NMDA，非NMDA，代谢性或合并类型的受体 NTS中的巴罗敏感神经元，尽管没有功能作用是 分配给受体。 差分分布的潜力 谷氨酸受体通过不同的时间课程启动反应，并且 对NTS神经元的影响可能有助于BP的差异控制。 因此，本研究的总体目的是检查静态和 NTS中压力感受器调节神经元的动态特征 可能有助于BP的差异控制，目的是确定 GLU受体亚型对NTS神经元排出的贡献 被特定的压力感受器亚型激活。 从 这些研究可以提供对差分控制机制的见解 在正常情况下血压以及该对照的改变如何 可能导致病理状态，包括高血压。