Noradrenaline excites and inhibits GABAergic transmission in parvocellular neurons of rat hypothalamic paraventricular nucleus.

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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 μM) 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 μM) increased sIPSC frequency by 256% in 59% of the neurons. This effect was blocked by prazosin (2–20 μM), the α1-adrenoceptor antagonist and mimicked by phenylephrine (10–100 μM), the α1-adrenoceptor agonist. However, in 33% of the neurons, NA decreased sIPSC frequency by 54%, and this effect was blocked by yohimbine (2–20 μM), the α2-adrenoceptor antagonist and mimicked by clonidine (50 μM), the α2-adrenoceptor agonist. The Na+ channel blocker, tetrodotoxin (0.1 μM) blocked the α1-adrenoceptor–mediated effect, but not the α2-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 α1-adrenoceptors and the decrease in sIPSC frequency via axonal terminal α2-adrenoceptors on the presynaptic GABAergic neurons.