Respiratory pattern is generated in the brainstem by a complex of interconnected pontine and medullary nuclei. Respiratory pattern is normally set to operate with maximum efficiency for optimal blood gas exchange. In some instances however, the behavioral and arousal state of the subject may trigger a change in respiratory pattern that is dissociated from functional needs of the body. Panic attacks and fear are examples of behavioral states in which modulation of breathing pattern may result in an overall reduction in ventilatory function. Heightened anxiety or panic attacks affect millions of Americans and are associated with increased morbidity as well as increased medical resource utilization. Yet, the specific regions of the brain that contribute to sustained ventilatory drive during fear or panic are not well defined. Our long-range goal is to more clearly define the role of the central nervous system in the generating the cardiorespiratory response ? to fear or anxiety. The central hypothesis to be tested by this proposal is that neurons in dorsal pons (the lateral parabrachial nucleus; LPBN) play a critical role in relaying respiratory responses evoked from the dorsal medial hypothalamus (DMH) to the respiratory cell groups in the medulla. We will test our hypothesis using a combination of immunohistochemistry, neuropharmacology, behavioral and extracellular recording techniques.
Five specific aims are proposed:
Specific Aim 1 : To identify the role of the dorsal periaqueductal gray (dPAG) in mediating respiratory responses evoked by DMH stimulation.
Specific Aim 2 : To identify the role of the LPBN in mediating the respiratory response evoked by DMH stimulation.
Specific Aim 3 : To identify the origin of neurons with descending projections to the LPBN that are activated by DMN stimulation or fear-inducing stimuli.
Specific Aim 4 : To identify whether neuronal activity in the medial versus commissural nucleus of the solitary tract (NTS) attenuates the respiratory response to DMN stimulation.
Specific Aim 5 : To identify the origin of neurons activated by DMN stimulation with descending projections to the NTS. The results of these studies will be innovative because they will be the first to investigate the role of the pons in the descending pathway through which the respiratory component of the hypothalamic """"""""defense"""""""" response is mediated. Furthermore, the results of this study will provide new insights into understanding of the role of supramedullary structures in modulating respiratory timing. ? ?
