It is well known that area postrema neurons augment baroreflex and cardiopulmonary reflex regulation of the sympathetic nervous system. Very little is known regarding the CNS sites, mechanisms, and pharmacology involved in the augmentation. Our goal is to identify the central pathways, mechanisms, and neurotransmitter/neuromodulators whereby area postrema neurons augment baroreflex and cardiopulmonary reflex control of sympathetic nerve activity. We propose that augmentation occurs early in the afferent pathways at the level of nucleus tractus solitarius (NTS) where area postrema neurons increase the sensitivity of NTS neurons to inputs from baroreceptor or cardiopulmonary afferents. We showed electrophysiologically that area postrema and aortic baroreceptor afferents converge onto the same neurons in the NTS and interact in a facilitatory manner. Same was true for area postrema and vagal afferents, suggesting a basis for area postrema augmentation of cardiopulmonary receptor-mediated sympathoinhibition. We propose to extend this work to test the following specific hypotheses: 1. Activation of area postrema neurons augments cardiopulmonary receptor-evoked sympathoinhibition increasing the responsiveness of NTS cells to input from cardiopulmonary receptors. 2. Augmentation by area postrema neurons of the central processing of both baroreceptor and cardiopulmonary receptor afferent input by NTS neurons is mediated by a direct route from area postrema to the NTS and by an indirect route from area postrema to the parabrachial nucleus (PBN) and back to the NTS. 3. Augmentation involves both glutamatergic and noradrenergic synapses in NTS. Hypotheses will be tested in pentobarbital-anesthetized rabbits.
These aims are: 1. determine whether excitation of area postrema neurons augments the responsiveness of left atrial receptor-sensitive neurons in the NTS to activate the left atrial receptors; 2. determine whether interruption of synaptic activity in PBN alters the ability of area postrema neurons to evoke spikes from NTS neurons and/or to augment the processing by those NTS neurons of either left atrial receptor or baroreceptor input; 3. determine whether PBN neurons that receive excitatory inputs from area postrema send efferent projections to the NTS; 4. determine the neurotransmitter/neuromodulator(s) by which stimulation of area postrema neurons augment responsiveness of myelinated left atrial receptor- sensitive NTS neurons to left atrial receptor activation and of baroreceptor-sensitive cells to baroreceptor activation; 5. determine whether area postrema neurons which project to the NTS (where left atrial receptor or baroreceptor afferents terminate) or to the PBN are excited by local injections of vasopressin, which is implicated at acting within the area postrema to augment baroreflex and cardiopulmonary reflex function.
|Hallam, K M; Edirisinghe, I; Balasuriya, U B R et al. (2007) Effects of mitral regurgitation on the reflex diuresis to pulmonary lymphatic obstruction in rabbits. Exp Lung Res 33:259-75|
|McCormick, K M; Bravo, E M; Kappagoda, C T (2005) Role of adrenergic receptors in the reflex diuresis in rabbits during pulmonary lymphatic obstruction. Exp Physiol 90:341-7|
|Ma, A A; Ravi, K; Bravo, E M et al. (2004) Effects of gadolinium chloride on slowly adapting and rapidly adapting receptors of the rabbit lung. Respir Physiol Neurobiol 141:125-35|
|McCormick, K M; Gunawardena, S; Ravi, K et al. (2004) Role of nitric oxide in the reflex diuresis in rabbits during pulmonary lymphatic obstruction. Exp Physiol 89:487-96|
|Guo, Z-L; Longhurst, J C (2003) Activation of nitric oxide-producing neurons in the brain stem during cardiac sympathoexcitatory reflexes in the cat. Neuroscience 116:167-78|
|Gunawardena, S; Ravi, K; Longhurst, J C et al. (2002) Responses of C fiber afferents of the rabbit airways and lungs to changes in extra-vascular fluid volume. Respir Physiol Neurobiol 132:239-51|
|Symons, J D; Gunawardena, S; Kappagoda, C T et al. (2001) Volume overload left ventricular hypertrophy: effects on coronary microvascular reactivity in rabbits. Exp Physiol 86:725-32|
|Li, P; Tjen-A-Looi, S; Longhurst, J C (2001) Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic response in cats. Auton Neurosci 89:38-47|
|Liu, Z; Chen, C Y; Bonham, A C (2000) Frequency limits on aortic baroreceptor input to nucleus tractus solitarii. Am J Physiol Heart Circ Physiol 278:H577-85|
|Daniels, J W; Stebbins, C L; Longhurst, J C (2000) Hemodynamic responses to static and dynamic muscle contractions at equivalent workloads. Am J Physiol Regul Integr Comp Physiol 279:R1849-55|
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