• Kaufman, Marc (PI)

Project: Research project

Project Details


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.
Effective start/end date10/1/966/30/98


  • National Heart, Lung, and Blood Institute

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