Noradrenaline Excites and Inhibits GABAergic Transmission in Parvocellular Neurons of Rat Hypothalamic Paraventricular Nucleus

Abstract

Noradrenaline (NA) is a major neurotransmitter that regulates many neuroendocrine and sympathetic autonomic functions of the hypothalamic paraventricular nucleus (PVN). Previously NA has been shown to increase the frequency of excitatory synaptic activity of parvocellular neurons within the PVN, but little is known about its effects on inhibitory synaptic activity. In this work, we studied the effects of NA (1-100 microM) on the spontaneous inhibitory synaptic currents (sIPSC) of type II PVN neurons in brain slices of the rat using the whole cell patch-clamp technique. Spontaneous IPSCs were observed from most type II neurons (n = 121) identified by their anatomical location within the PVN and their electrophysiological properties. Bath application of NA (100 microM) increased sIPSC frequency by 256% in 59% of the neurons. This effect was blocked by prazosin (2-20 microM), the alpha(1)-adrenoceptor antagonist and mimicked by phenylephrine (10-100 microM), the alpha(1)-adrenoceptor agonist. However, in 33% of the neurons, NA decreased sIPSC frequency by 54%, and this effect was blocked by yohimbine (2-20 microM), the alpha(2)-adrenoceptor antagonist and mimicked by clonidine (50 microM), the alpha(2)-adrenoceptor agonist. The Na(+) channel blocker, tetrodotoxin (0.1 microM) blocked the alpha(1)-adrenoceptor-mediated effect, but not the alpha(2)-adreonoceptor-mediated one. Both of the stimulatory and inhibitory effects of NA on sIPSC frequency were observed in individual neurons when tested with NA alone, or both phenylephrine and clonidine. Furthermore, in most neurons that showed the stimulatory effects, the inhibitory effects of NA were unmasked after blocking the stimulatory effects by prazosin or tetrodotoxin. These data indicate that tonic GABAergic inputs to the majority of type II PVN neurons are under a dual noradrenergic modulation, the increase in sIPSC frequency via somatic or dendritic alpha(1)-adrenoceptors and the decrease in sIPSC frequency via axonal terminal alpha(2)-adrenoceptors on the presynaptic GABAergic neurons.

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

“…Depending on the receptor subtype expressed, NE has the capacity to either stimulate or depress neuronal activity (Han et al, 2002). For control purposes, we tested the effect of NE on mouse supraoptic nucleus and corroborated previous findings in the rat showing that NE was excitatory and evoked depolarizing actions (Armstrong et al, 1986;Boudaba et al, 2003).…”

Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus

“…Noradrenaline increases the frequency of IPSCs by activating the ␣ 1 -adrenoceptors on the soma, but decreases their frequency by activating the ␣ 2 -adrenoceptors (Chong et al 2004;Daftary et al 2000;Han et al 2002;Li et al 2005) and ␣ 1 -adrenoceptors on the terminal of GABAergic neurons (Chen et al 2006). These receptors were further identified as ␣ 1A/1L and ␣ 2A subtypes, respectively (Chong et al 2004).…”

Responses to GABA-A receptor blockade in the hypothalamic PVN are attenuated by local AT1 receptor antagonism

“…These include such classical transmitters as glutamate (18), acetylcholine (29), and norepinephrine (16) as well as neuropeptides like corticotrophin-releasing factor, met-enkephalin, and angiotensin II (ANG II) (14,23,27). Although many candidate sources of excitation are present in the PVN, this study focused on the role of ANG II in the response to removal of GABAergic inhibition.…”