Elsevier

Brain Research

Volume 807, Issues 1–2, 5 October 1998, Pages 61-69
Brain Research

Research report
Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic α2-adrenoceptors

https://doi.org/10.1016/S0006-8993(98)00732-XGet rights and content

Abstract

It has been shown that noradrenergic activation has great influence on the activities of hypothalamic supraoptic neurons. No direct evidence has been reported on the presynaptic effects of adrenoceptors in the actions of noradrenaline on supraoptic neurons, although postsynaptic mechanisms have been studied extensively. In the present study, we explored presynaptic effects of noradrenaline on the supraoptic neurons by measuring spontaneous inhibitory postsynaptic currents (IPSC) with the whole-cell patch-clamp technique. Noradrenaline reduced the frequency of IPSCs in a dose-dependent (10−9 to 10−3 M) and reversible manner. Noradrenaline did not affect the amplitude of IPSCs at concentrations of 10−9 to 10−5 M, but reduced the amplitude of IPSCs at high concentrations (10−4 and 10−3 M). The inhibitory effects of noradrenaline were mimicked by the α2-agonist clonidine (10−4 M), but not by the α1-agonist methoxamine (10−4 M) nor by the β-agonist isoproterenol (10−4 M). Moreover, the inhibitory effects of noradrenaline on IPSCs were blocked by the non-selective α antagonist phentolamine (10−4 M) or the selective α2-antagonist yohimbine (10−4 M), but not by the α1-antagonist prazosin (10−4 M). These results suggest that noradrenaline inhibits release of GABA from the presynaptic GABAergic terminals of the supraoptic neurons by activating presynaptic α2-adrenoceptors and such presynaptic mechanisms may play a role in the excitatory control of SON neurons by noradrenergic neurons.

Introduction

The neurosecretory functions of oxytocin and vasopressin neurons in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) are closely related to noradrenergic input. Morphologically, it was found that noradrenergic afferent innervating both the SON and the PVN 3, 34derive mainly from the medulla oblongata 14, 15, 16, 17, 29, 34, 43and form synaptic contacts with both vasopressin neurons and oxytocin neurons 23, 27, 35in the SON and the PVN. Functionally, noradrenergic afferents exert an excitatory action on the activities of hypothalamic magnocellular neurons 5, 11, 29, 30, 41. With intracellular recording, it has been demonstrated that noradrenaline induced depolarization of the membrane potential and increased the firing rate of SON neurons 31, 42. Depletion of central catecholamine resulted in the impairment of the neurosecretory function of the magnocellular neurons 24, 27. These lines of evidence suggest that noradrenergic innervation plays a crucial role in the function of hypothalamic magnocellular neurons.

While α1-adrenoceptors were reported to be the main receptors mediating the postsynaptic actions of noradrenaline on the activities of magnocellular neurons in the SON and the PVN 4, 31, 42, the existence of α2-adrenoceptors [1]and β-adrenoceptors [19]and their effects on the electrical activities of the magnocellular neurons 4, 41has also been reported in the two nuclei. These findings indicate that α2- and β-adrenoceptors may be involved in the actions of noradrenaline on the activities of hypothalamic magnocellular neurons besides α1-adrenoceptors.

It is known that GABAergic terminals account for about half of the synaptic terminals on the SON magnocellular neurons 6, 9, 22and that spontaneous IPSCs of SON neurons directly reflect the spontaneous release of GABA from the terminals of GABAergic neurons at the SON 12, 40. Noradrenergic afferents mainly terminate at the ventral dendritic area and the perinuclear zone [34], where abundant GABAergic soma and terminals have been identified [32]. Moreover, α2-adrenoceptors as heteroreceptors on non-adrenergic terminals has been found at serotonergic nerve endings [8], glutamatergic terminals [13], and GABAergic terminals [28]in the rat hypothalamus. These findings led us to study effects of noradrenaline on the activity of presynaptic GABAergic terminals in the SON. In the present study, we observed the effects of noradrenaline on IPSCs and analyzed the types of adrenoceptors mediating the effects of noradrenaline in thin punch out slices of rats [12]. The results showed that noradrenaline exerts inhibitory actions on IPSCs of the SON magnocellular neurons through α2-adrenoceptors.

Section snippets

Slice preparations

Young adult male Wistar rats (150–250 g) were stunned by a blow on the back of the neck and rapidly decapitated. The brains were quickly removed and cooled for approximately 1 min in a perfusion medium oxygenated with 95% O2–5% CO2 gas, containing (in mM): NaCl 124, KCl 5, KH2PO4 1.24, MgSO4 1.3, CaCl2 2.1, NaHCO3 25.9 and glucose 10 at 4°C. A block containing the hypothalamus was cut from the brain and was glued onto the stage of a vibratome-type slicer (DSK-2000; DSK, Kyoto, Japan). After the

Results

Spontaneous IPSCs were recorded from 108 SON magnocellular neurons. The frequency and amplitude of IPSCs ranged between 0.5 to 5.5 Hz (1.6±0.2 Hz, n=108) and between 10.6 to 41.3 pA (25.1±1.5 pA, n=108), respectively.

Discussion

In the present study, we found that noradrenaline markedly reduced the frequency of IPSCs recorded from SON neurons. These findings provide the first direct evidence that noradrenaline acting at presynaptic GABAergic terminals suppresses inhibitory synaptic inputs to SON neurons. As a decrease in inhibitory synaptic inputs would facilitate the electrical activity of postsynaptic neurons, the presynaptic inhibition of IPSCs may play a role in the excitatory effects of noradrenaline on the

Acknowledgements

This study was supported in part by grants-in-aid from the Ministry of Education, Sports, Science and Culture, Japan, to H.Y. (07507004 and 08457022) and to I.S. (09470020), and by a grant from Ajinomoto (Kawasaki, Japan) to H.Y.

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