Acute stress facilitates glutamatergic long-term potentiation of hypothalamic paraventricular nucleus magnocellular neurons via activation of β1-adrenergic receptors in rats in vivo

Acute stress enhances the activity of magnocellular neurons (MNs) by inducing long-term changes in excitatory inputs. We aim to investigate the mechanism underlying long-term potentiation (LTP) of glutamatergic inputs to paraventricular nucleus (PVN) MNs in stressed rats. Rats were subjected to multiple stressors and randomly assigned to control and stress groups. In some experiments, stressed rats received intracerebroventricular (i.c.v.) injections of the β-adrenergic receptor (AR) antagonist or the β1-AR antagonist. Excitatory postsynaptic currents evoked by electrical stimulation in hypothalamic slices were recorded from PVN MNs using an Axopatch 200B amplifier. LTP of glutamatergic inputs to MNs was induced by electrical stimulation trains (100 Hz, 100 pulses, three times). Biocytin staining and immunohistochemistry were used to characterize the morphology of recorded neurons and detect β1-AR expression. Blockade of gamma-aminobutyric acid receptor, tetanic stimulation-induced glutamatergic LTP in MNs of nonstressed rats, which was significantly augmented in stressed rats. Blocking N-methy-D-aspartate receptors abolished LTP in nonstressed rats but revealed a novel LTP in stressed rats. I.c.v. administration of propranolol, or CGP 20712, before the stress procedure abolished this novel LTP in stressed rats. In contrast, administration of norepinephrine or a selective β1-AR agonist, dobutamine triggered the novel LTP in nonstressed rats. The novel LTP in stressed rats was abolished by intracellular inhibition of protein kinase A (PKA). β1-AR immunoreactivity was detected in PVN MN areas. Acute stress enhances the β1-AR/PKA signaling, leading to long-term modifications of glutamatergic inputs in the hypothalamic PVN MNs in rats in vivo.