Activation of subfornical organ neurons in rats through pre- and postsynaptic α-adrenoceptors

Abstract

(NA) and its analogs on subfornical organ (SFO) neurons in rat slice preparations were investigated by using whole cell patch-clamp recording. In the current-clamp mode, the application of NA at 10 -100 M produced membrane depolarization (63%, 17 responsive neurons/27 neurons tested) and hyperpolarization (22%, 6/27 neurons). In the voltage-clamp mode, NA application at 1-100 M produced inward currents (69%, 42/61 neurons) and outward currents (23%, 14/61 neurons). These currents remained in the presence of TTX or both glutamate and GABA receptor antagonists. In most of the neurons (25/31 neurons) showing inward currents in the presence of NA, the membrane conductance was not changed by voltage ramps or hyperpolarizing pulse stimulation. Similar responses were obtained by the application of the ␣ 1-agonist phenylephrine. The phenylephrineinduced inward currents were inhibited by the ␣1-antagonist prazosin. The ␣ 2-agonist clonidine decreased the frequency of spontaneous GABAergic inhibitory postsynaptic currents (4/10 neurons). In addition, RT-PCR assay and immunohistochemical staining showed the existence of ␣ 1-adrenoceptors in the SFO. The results suggest that SFO neurons in rats are activated postsynaptically through ␣ 1-adrenoceptors and that the activation is enhanced by suppressing GABAergic inhibitory synaptic inputs through presynaptic ␣ 2-adrenoceptors. patch clamp; slice preparation; noradrenaline THE SUBFORNICAL ORGAN (SFO), which juts ventrally from the hippocampal commissura into the third cerebral ventricle, is a circumventricular organ. The SFO receives various neural inputs from brain regions, whereas it lacks a blood-brain barrier and has an abundant vascular supply (for a review, see Ref. 14). From these properties, the SFO has been thought to possess various sensors for neurotransmitters and blood-and cerebrospinal fluid-borne substances, and subsequently to control body fluid balance and the cardiovascular system (for reviews, see Refs. 8 and 15). In fact, angiotensinergic, cholinergic, and hypertonic activation of SFO neurons elicits water intake (23) and vascular responses, and increases vasopressin release from the posterior pituitary (11,12). Noradrenaline (NA), which is released from catecholaminergic fibers and the adrenal medulla, may be one of such bioactive substances affecting SFO neurons. The catecholaminergic neurons in the A1 and A2 areas of the medulla project directly to various brain regions, including the SFO (3, 10). The NA level in the region of the SFO is increased by hemorrhage, whereas it is decreased by an elevation in arterial pressure (26). The peripheral baroreceptor information may be transmitted from the nucleus of the solitary tract to the SFO through ␣-adrenoceptors (16, 25). Further, microinjection of NA into the SFO increases water intake (17). Thus NA at the level of the SFO may play an important role in the regulation of cardiovascular function and body fluid homeostasis. However, little is known about whether the SFO neurons themselves are directly affec...

Norepinephrine Suppresses Gonadotropin-Releasing Hormone Neuron Excitability in the Adult Mouse

“…If a good quality recording was still possible after this, tests were made examining the presence of multiple adrenergic receptors and/or the effects of prazosin the α1-aderenergic receptor antagonist (10 µM). The concentrations of agonists and antagonists used in this study have been proven to be effective in previous electrophysiolgical experiments (28, 29).…”