Zhang Yi-Dan, Weng Wen-Cai, Liu Yang, Gao Jun-Tao, Li Yu-Zi, Chu Chun-Ping, Qiu De-Lai
Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City.
Department of Neural Circuit, Institute of Brain Science.
Neuroreport. 2025 Oct 1;36(14):847-855. doi: 10.1097/WNR.0000000000002205. Epub 2025 Jul 24.
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.
急性应激通过诱导兴奋性输入的长期变化来增强大细胞神经元（MNs）的活性。我们旨在研究应激大鼠室旁核（PVN）MNs谷氨酸能输入的长时程增强（LTP）的潜在机制。
将大鼠置于多种应激源下，并随机分为对照组和应激组。在一些实验中，应激大鼠接受脑室内（i.c.v.）注射β-肾上腺素能受体（AR）拮抗剂或β1-AR拮抗剂。使用Axopatch 200B放大器从PVN MNs记录下丘脑切片中电刺激诱发的兴奋性突触后电流。通过电刺激串（100 Hz，100个脉冲，三次）诱导MNs谷氨酸能输入的LTP。使用生物素染色和免疫组织化学来表征记录神经元的形态并检测β1-AR表达。
阻断γ-氨基丁酸受体，强直刺激可诱导非应激大鼠MNs中的谷氨酸能LTP，在应激大鼠中显著增强。阻断N-甲基-D-天冬氨酸受体可消除非应激大鼠中的LTP，但在应激大鼠中揭示了一种新的LTP。在应激程序前i.c.v.给予普萘洛尔或CGP 20712可消除应激大鼠中的这种新LTP。相反，给予去甲肾上腺素或选择性β1-AR激动剂多巴酚丁胺可在非应激大鼠中触发新的LTP。应激大鼠中的新LTP通过细胞内抑制蛋白激酶A（PKA）而被消除。在PVN MN区域检测到β1-AR免疫反应性。
急性应激增强β1-AR/PKA信号传导，导致体内大鼠下丘脑PVN MNs中谷氨酸能输入的长期改变。
