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Brainstem control of blood pressure in conscious rodents

脑干对清醒啮齿动物血压的控制

基本信息

批准号：
9127736
负责人：
Ian Christopher Wenker
金额：
$ 5.61万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-30 至 2017-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127736
关键词：
Accounting Acute Anesthesia procedures Animals Area Blood Pressure Brain Brain Stem Brain region Breathing Cardiovascular Diseases Carotid Body Cause of Death Cells Cessation of life Chimeric Proteins Conscious Data Disease Environmental air flow Esthesia Genetic Genetic Recombination Glutamates Goals Health Hemorrhage Human Hypercapnia Hypertension Hypothalamic structure Hypoxia Kidney Maintenance Mammals Measures Methods Mus Nerve Neuraxis Neurologic Neurons Nucleus solitarius Organ Pathology Pathway interactions Peripheral Phenotype Physiological Population Population Heterogeneity Preparation Property Rattus Reflex action Regulation Research Rest Rodent Role Sensory Slice Sodium Spinal Cord Stress Sympathetic Nervous System System Techniques Testing Time Tissues Transgenic Mice Transgenic Organisms United States Viral Vector Work adeno-associated viral vector awake blood pressure regulation brain pathway design hypothalamic pituitary axis in vivo loss of function mind control mortality neural circuit new technology novel optogenetics recombinase research study sensory input stressor vector

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the United States today. Hypertension is believed to account to 40% of this mortality. The central nervous system contributes to resting blood pressure, mainly through the sympathetic nervous system, and many forms of hypertension are believed to have a neurological component. How the neural circuitry of the brain controls blood pressure is incompletely understood. Generalized regions of the brain are known to be important, but the specific types of neurons involved, and what they do have been difficult to determine. The objective of the proposed research is to determine the neural circuits in the brain that are responsible for blood pressure control at the cellular level. The experiments will allow for identification and functiona characterization of unique neuronal groups involved in blood pressure control, the second-order neurons of the nucleus of the solitary tract and hypothalamus projecting C1 neurons. The design utilizes state-of-the-art transgenic techniques and physiological recording methods enabling experiments to be performed in conscious, unrestrained animals. The C1 neurons are a population of catcholaminergic neurons localized to the rostral ventrolateral medulla that have been implicated in blood pressure control for decades. Significant research has established C1 neurons are activated by numerous stressors, are likely important for the peripheral chemoreflex and may provide for resting sympathetic tone. However, acute loss-of-function of C1 neurons, to confirm their role in blood pressure maintenance, has not been achieved in conscious animals. In addition, there exist at least two subpopulations of C1 neurons; those that project to the spinal cord and those that project to the hypothalamus, which may have differential effect on blood pressure, but have yet to be examined physiologically. In Aim 1 I propose experiments that allow for C1 neuron-specific acute inhibition under resting and hypoxic conditions, and in Aim 2 a novel transgenic approach to functionally dissect spinally-projecting and hypothalamic-projecting C1 neurons and their roles in BP control. The second-order neurons of the nucleus of the solitary tract receive inputs from various sensory organs, and relay this information throughout the brainstem. There are numerous sensory inputs that converge in the same area, making it difficult to functionally dissect these second-order neurons. The peripheral chemoreflex, sensation of arterial hypoxia and hypercapnia, is particularly important for blood pressure control and hypertension pathology. Previous experiments have been able to identify second-order neurons responsible for the peripheral chemoreflex, however the full extent of their projections and physiological capabilities are still unknown. In Aim 3 of this proposal, I wil use a new technology that will allow for genetic targeting of the hypoxia-sensitive neurons of the NTS to identify and functionally confirm their projections.