TY - JOUR
T1 - Regulation of synaptic inputs to paraventricular-spinal output neurons by α2 adrenergic receptors
AU - Li, De Pei
AU - Atnip, Lindsay M.
AU - Chen, Shao Rui
AU - Pan, Hui Lin
PY - 2005/1
Y1 - 2005/1
N2 - 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 α2 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 μM clonidine, an α2 receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 μM 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 α2 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 α2A receptor and GABA immunoreactivities were co-localized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of α2 adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic α2 receptors function as heteroreceptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
AB - 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 α2 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 μM clonidine, an α2 receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 μM 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 α2 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 α2A receptor and GABA immunoreactivities were co-localized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of α2 adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic α2 receptors function as heteroreceptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
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U2 - 10.1152/jn.00564.2004
DO - 10.1152/jn.00564.2004
M3 - Article
C2 - 15356178
AN - SCOPUS:16644385117
SN - 0022-3077
VL - 93
SP - 393
EP - 402
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
IS - 1
ER -