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.

Adrenalectomy potentiates noradrenergic suppression of GABAergic transmission in parvocellular neurosecretory neurons of hypothalamic paraventricular nucleus. J Neurophysiol 99: 514 -523, 2008. First published November 21, 2007 doi:10.1152/jn.00568.2007. Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by ␣ 2A -and ␣ 1A/1L -adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 M), a ␣ 2A -adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the ␣ 2A -adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.