Abstract
The magnocellular neurosecretory cells (MNCs) of the hypothalamic paraventricular nucleus (PVN) integrate incoming signals to secrete oxytocin (OT), and vasopressin (VP) from their nerve terminals in the posterior pituitary gland. In the absence of gamma-aminobutyric acid A (GABAA) and cannabinoids 1 (CB1) receptor activity, we used whole-cell patch-clamp recording, single-cell reverse transcription-multiplex polymerase chain reaction (SC-RT-mPCR), biocytin histochemistry and pharmacological methods to examine the mechanism of high frequency stimulus (HFS, 100 Hz)-induced long-term potentiation (LTP) at glutamatergic synapses in the PVN MNCs of juvenile male rats. Our results showed that HFS-induced LTP at glutamatergic synapses was accompanied by a decrease in the paired-pulse ratio (PPR) of the PVN MNCs. In these MNCs, HFS-induced LTP persisted in the presence of a group 1 metabotropic glutamate receptor (mGluR1) antagonist; however, it was abolished by an N-methyl-D-aspartic acid (NMDA) receptor blocker. Notably, HFS-induced LTP in the PVN MNCs was completely prevented by a nitric oxide synthase (NOS) inhibitor. The application of an NO donor not only induced the LTP of excitatory glutamatergic inputs in the PVN MNCs, but also occluded the HFS-induced LTP in these MNCs. Moreover, HFS-induced LTP in the PVN MNCs was also abolished by a specific protein kinase A (PKA) inhibitor, KT5720. SC-RT-mPCR analysis revealed that 64.5% (62/96) of MNCs expressed OT mRNA. Our results indicate that a HFS can induce an NMDA receptor and NO cascades dependent on presynaptic glutamatergic LTP in the PVN MNCs via a PKA signaling pathway.
Highlights
The hypothalamic paraventricular nucleus (PVN) is a functionally heterogeneous nucleus consisting of various groups of neurons, which participate in parvocellular neuroendocrine functions as well as magnocellular neuroendocrine and parvocellular autonomic functions
Consistent with that study (Kiedrowski et al, 1992), our results suggest that high frequency stimulation (HFS) delivery activated N-methyl-D-aspartic acid (NMDA) receptors, which enhanced nitric oxide (NO) production in the PVN magnocellular neurosecretory cells (MNCs) of juvenile male rats
We found that HFS induced long-term potentiation (LTP) at glutamatergic synapses accompanied with a decrease in pairedpulse ratio in the PVN MNCs
Summary
The hypothalamic paraventricular nucleus (PVN) is a functionally heterogeneous nucleus consisting of various groups of neurons, which participate in parvocellular neuroendocrine functions (e.g., the stress response and thyroid hormone control) as well as magnocellular neuroendocrine and parvocellular autonomic functions. Paraventricular nucleus MNCs receive afferent inputs from the median preoptic nucleus (MnPo), subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), brainstem nuclei (Swanson and Sawchenko, 1980), and other intrahypothalamic nuclei (Csaki et al, 2000) These afferent input fibers contain various neurotransmitters, such as excitatory glutamate (van den Pol et al, 1990) and inhibitory gammaaminobutyric acid (GABA) (Decavel and Van den Pol, 1990). The brief, high frequency bursts of spike firing exhibited by OTergic neurons prior to milk ejection are thought to result from afferent volleys of glutamatergic excitatory postsynaptic potentials (EPSPs) (Jourdain et al, 1998). Endocannabinoids (eCBs) released from PVN MNCs can transiently depress the release of glutamate from excitatory terminals and influence synaptic plasticity in PVN MNCs (Iremonger et al, 2011)
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