A Nitric Oxide-Dependent Presynaptic LTP at Glutamatergic Synapses of the PVN Magnocellular Neurosecretory Cells in vitro in Rats

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 (GABA A ) 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.

Nitric oxide synthase contributes to the maintenance of LTP in the oxytocin–mRFP1 neuron of the rat hypothalamus

“…Researchers have used several protocols to induce LTP in the hypothalamus. High‐frequency stimulation (HFS; 100 pulses, thrice, 10 s intervals) and optogenetic protocols induce LTP in the hypothalamus 13,14,32,33 . In the present study, we used pairing protocol stimulation.…”

“…High-frequency stimulation (HFS; 100 pulses, thrice, 10 s intervals) and optogenetic protocols induce LTP in the hypothalamus. 13,14,32,33 In the present study, we used pairing protocol stimulation. After stimulation, LTP was induced in the postsynaptic neurons of the ACC, which are patched neurons.…”

“…11 LTP inhibition in these regions produces analgesic and anxiolytic effects. 10,11 LTP induction has been reported in the hypothalamus 13,14 ; however, the neurons in which LTP occurs have not been clearly identified and characterized. Researchers have not yet examined LTP in hypothalamic OXT-ergic neurons.…”

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

“…A total of 79 PVN neurons from 54 rats were identi ed the PVN MNCs by whole-cell patch clamp recording technique and biocytin staining method [5,7,50,51]. Under current-clamp recording conditions, these putative MNCs exhibited a transient outward recti cation in response to a series of depolarizing current pulses delivered at a hyperpolarized membrane (Fig.…”

Effect of Moderate Intensity Exercise on Synaptic Vesicle Transporter and Antioxidant Enzyme Expression in High Fat Diet Fed 3xTg Mice

“…실제로 시냅스 및 수상 돌기 가시(dendritic spine) 손실은 응집된 Aβ plaque에 근접하여 악화 되는 것으로 나타났으며 [15], 심각할 경우 학습과 기억을 비롯한 인지 기능 장애에 영향을 미치는 것으로 보고되고 있다. 그 중 gamma-ami-nobutyric acid (GABA)와 glutamate는 중추신경계의 대표적인 신경전 달물질로서 시냅스에서의 신경전달 [16], 세포의 생존과 성장 [17,18] 및 시냅스 장기강화(Long term potentiation) [19,20] (Fig. 4B-D).…”