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Regulation of synaptic inputs to paraventricular-spinal output neurons by alpha2 adrenergic receptors.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2005 Jan; Vol. 93 (1), pp. 393-402. Date of Electronic Publication: 2004 Sep 08. - Publication Year :
- 2005
-
Abstract
- Neurons in the paraventricular nucleus (PVN) that project to the brain stem and spinal cord are important for autonomic regulation. The excitability of preautonomic PVN neurons is controlled by the noradrenergic input from the brain stem. In this study, we determined the role of alpha(2) adrenergic receptors in the regulation of excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) were recorded using whole cell voltage-clamp techniques on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Bath application of 5-20 muM clonidine, an alpha(2) receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 microM clonidine significantly decreased the frequency (from 2.68 +/- 0.41 to 1.22 +/- 0.40 Hz) but not the amplitude of miniature IPSCs (mIPSCs), and this effect was blocked by the alpha(2) receptor antagonist yohimbine. Furthermore, clonidine increased the paired-pulse ratio of evoked IPSCs from 1.25 +/- 0.05 to 1.61 +/- 0.08 (P < 0.05). On the other hand, clonidine had little effect on evoked glutamatergic EPSCs, mEPSCs, and the paired-pulse ratio of evoked EPSCs in most labeled cells examined. Additionally, immunofluorescence labeling revealed that the alpha(2A) receptor and GABA immunoreactivities were co-localized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of alpha(2) adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic alpha(2) receptors function as heteroreceptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
- Subjects :
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology
Adrenergic alpha-Agonists pharmacology
Adrenergic alpha-Antagonists pharmacology
Animals
Bicuculline pharmacology
Brain Stem physiology
Clonidine pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Antagonists pharmacology
Excitatory Postsynaptic Potentials physiology
Fluorescent Antibody Technique methods
GABA Antagonists pharmacology
In Vitro Techniques
Neural Inhibition physiology
Neurons drug effects
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Synapses drug effects
Synaptophysin metabolism
Time Factors
Yohimbine pharmacology
gamma-Aminobutyric Acid metabolism
Afferent Pathways physiology
Neurons physiology
Paraventricular Hypothalamic Nucleus cytology
Receptors, Adrenergic, alpha-2 physiology
Spinal Cord physiology
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 93
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 15356178
- Full Text :
- https://doi.org/10.1152/jn.00564.2004