Pharmacology and physiology and CNS autonomic cardiovascular control
Emotional stress has been causally linked to a wide variety of human disease and disorders, including hypertension, sudden death, increased susceptibility to infection, and gastrointestinal disturbances. In all mammals, the hypothalamus has long been thought to represent the site of a neural command center capable of triggering the characteristic physiologic changes seen in stress. However the precise location and identity of the relevant hypothalamic neurons has been unknown. Work from this laboratory performed in rats and spanning the past two decades has shown that neurons in a nearby but distinct region - the region of the dorsomedial hypothalamus, or DMH - may serve this function. Activation of the DMH results in cardiovascular, neuroendocrine, intestinal motility, respiratory and behavioral changes resembling those typically seen in emotional stress in rats. Conversely, inhibition of neuronal activity in the same region can prevent stress induced cardiovascular changes and exerts an "anti-anxiety" effect. More recently, we have shown that the cardiac stimulation resulting from activation of the DMH or from exposure to experimental stress results from activation of a neural "relay" in the raphe pallidus, a brainstem region never previously suspected of playing a role in stress. An important consequence of this knowledge has been our ability to identify the specific location of the key hypothalamic neurons responsible for cardiac stimulation seen in emotional stress. Furthermore, intriguing new findings from studies now in progress suggest that this neural circuit from the DMH to the raphe pallidus also plays a key role in temperature regulation and fever - another novel and unexpected finding. Because hypothalamic mechanisms are generally highly conserved across different mammalian species, these findings in rats are likely to have parallels in humans. In fact, recent findings suggest a connection between the mechanisms we have characterized and panic disorder, a relatively common clinical condition about which almost nothing is known.
Because so little is known about the DMH or the raphe pallidus relative to the important roles suggested by our results, many basic questions remain to be answered. Research now in progress is aimed at answering some of these questions and extending our previous findings. Studies both planned and in progress will characterize the neurons involved in these circuits and explore the modes of neural signaling at key nodal points that may be responsible for the generation of the physiological changes seen in stress and for the febrile response.
Cardiovascular Diseases, Hypertension, Italy, Nervous System, Neuroscience, Neurotransmitters, Pharmacology, Physical Senses, Other, Physiological Processes, Physiology, Vertebrate, Receptors
