REGULATION OF BARORECEPTOR AFFERENT TRANSMISSION

Project: Research project

Project Details

Description

DESCRIPTION: Activity and time-dependent integration of baroreceptor information is the first step in the normal regulation of the cardiovascular reflex function and alterations of the synaptic transmission between the baroreceptors afferents and NTS neurons has been suggested to contribute to inappropriate reflex control of sympathetic outflow. Although high-frequency stimulation of baroreceptor afferents has been shown to decrease evoked NTS excitatory potentials and results in a right-ward shift in the baroreceptor reflex, the cellular mechanisms underlying activity-dependent alterations in the signal transduction between baroreceptor afferents and NTS neurons are unknown. It is thought that the maintenance of synaptic transmission over a wide range of frequency stimulations requires that nerve terminals maintain pools of synaptic vesicles in reserve which can be recruited to the active exocytosis zones during periods of intense activity. In the case of baroreceptor/NTS synapses, failure to recruit vesicles to the baroreceptor exocytosis zones during periods of high activity could reasonable be hypothesized to lead to decreased synaptic efficacy, decreased NTS postsynaptic activation and ultimately allowing an increase in sympathetic outflow. Recently, metabotropic glutamate receptors (mGluRs) and neuropeptide Y (NPY) receptors have been suggested to potentially play important role in the regulation of neurotransmitter exocytosis at glutamatergic synapses. Activation of these receptors has been suggested to negatively feedback onto the presynaptic membrane to inhibit neurotransmitter release. Vesicle exocytosis is known to be regulated by calcium influx dependent second messenger systems and the phosphorylation and dephosphorylation of synaptic terminal associate proteins such as synapsin I(a,b), synapsin II(a,b). The proposed studies will test the general hypothesis that activation of mGluR and NPY receptors inhibits aortic baroreceptor synaptic vesicle exocytosis and endocytosis and contributes to the frequency-dependent inhibition of NTS synaptic activity. In addition, it is proposed that activation of these receptors influences presynaptic function in part by modulating the phosphorylation state of the synaptic vesicle proteins synapsin I and II which are known to be involved in synaptic vesicle release. There are four major and distinct aims: 1) To evaluate aortic baroreceptor vesicle exocytosis and endocytosis during activation of mGluRs. 2) To evaluate aortic baroreceptor vesicle exocytosis and endocytosis during activation of NPY receptors. 3) To examine phosphorylation of the synaptic terminal proteins synapsin I and II in visceral afferent neurons during activation of mGluR and NPY receptors. 4) To determine the role of NPY and mGluR during frequency-limited activation of afferent evoked NTS neuronal activity. These studies are expected to yield specific information concerning cellular mechanisms involved in the regulation of baroreceptor afferent neurotransmission.
StatusFinished
Effective start/end date12/19/9711/30/09

Funding

  • National Institutes of Health: $143,008.00
  • National Institutes of Health: $21,622.00
  • National Institutes of Health: $151,719.00
  • National Institutes of Health: $147,299.00
  • National Institutes of Health
  • National Institutes of Health: $235,628.00
  • National Institutes of Health: $209,785.00
  • National Institutes of Health: $182,332.00
  • National Institutes of Health: $216,051.00

ASJC

  • Medicine(all)

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