Acute stress facilitates glutamatergic long-term potentiation in PVN magnocellular neurons through beta-adrenergic receptor/PKA cascade in vitro in rats

Abstract

Abstract Acute stress alternates the hypothalamic paraventricular nucleus (PVN) magnocellular neuronal activity through modulation of excitatory and inhibitory synaptic inputs, leading to abnormal secretion of oxytocin (OT) and vasopressin (VP). However, mechanism of acute stress modulates the glutamatergic long-term potentiation (LTP) in PVN magnocellular neuroendocrine cells (MNCs) is unclear. We here investigated the effect of acute stress on the glutamatergic LTP of PVN MNCs, by whole-cell patch-clamp recording with biocytin staining and pharmacological methods. Delivery of high frequency stimulation (HFS) induced a glutamatergic LTP accompanied with a decrease in paired-pulse ratio in PVN MNCs, which was significantly enhanced in acute stress rats. Blockade of N-methyl-D-aspartate receptors (NMDAR) activity abolished the LTP of PVN MNCs in control group, but reveal a NMDAR-independent LTP in acute stress group. The NMDAR-independent LTP of PVN MNCs in stress rats was abolished by a β-AR inhibitor, propranolol, but not by an α-AR inhibitor, Phentolamine. The NMDAR-independent LTP of PVN MNCs in stress rats was abolished by bath application of a potent protein kinase A (PKA) inhibitor, KT5720 (200 nM), but not by a PKC inhibitor. Moreover, postsynaptic blockade of PKA completely prevented the HFS-induced glutamatergic LTP in PVN MNCs of stress rats. These results indicate that acute stress triggers an NMDAR-independent glutamatergic LTP of the PVN MNCs through a postsynaptic β-AR/PKA signaling pathway, resulting in an enhancement of an NMDAR-dependent presynaptic LTP in vitro in rats. The results suggest that acute stress upregulates OT and VP secretion by enhancing the excitatory glutamatergic LTP of PVN MNCs.