Adrenergic Receptors

Neurons in the paraventricular nucleus (PVN) that project to the brainstem and spinal cord are important for autonomic regulation. The excitability of pre-autonomic PVN neurons is controlled by the noradrenergic input from the brainstem. In this study, we determined the role of " 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 :M clonidine, an " 2 receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 :M clonidine significantly decreased the frequency (from 2.68 ± 0.41 to 1.22 ± 0.40 Hz) but not the amplitude of mIPSCs and this effect was blocked by the " 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 " 2A receptor and GABA immunoreactivities were colocalized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of " 2 adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic " 2 receptors function as heterorecptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.