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在大鼠海马 CA3 区的中间神经元和锥体神经元上表达 TrkB 受体的功能。

Functional expression of TrkB receptors on interneurones and pyramidal cells of area CA3 of the rat hippocampus.

机构信息

Departamento de Farmacobiología, Cinvestav Sur, México City, México.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, United States.

出版信息

Neuropharmacology. 2021 Jan;182:108379. doi: 10.1016/j.neuropharm.2020.108379. Epub 2020 Oct 30.

Abstract

The dentate gyrus and hippocampal area CA3 region of the mammalian brain contains the highest levels of brain-derived neurotrophic factor (BDNF) and its canonical membrane receptor, tropomyosin-related kinase B (TrkB). Therefore, the present study examines the expression and physiological responses triggered by activation of TrkB on hippocampal area CA3 interneurones and pyramidal cells of the rat hippocampus. Triple immunolabelling for TrkB, glutamate decarboxylase 67, and the calcium-binding proteins parvalbumin, calbindin or calretinin confirms the somatic expression of TrkB in all CA3 sublayers. TrkB-positive interneurones with fast-spiking discharge are restricted to strata oriens and lucidum, whereas regular-spiking interneurones are found in the strata lucidum, radiatum and lacunosum-moleculare. Activation of TrkB receptors with 7,8-dihydroxyflavone (DHF) modulates amplitude and frequency of spontaneous synaptic currents recorded from CA3 interneurones. Furthermore, the isolated excitatory postsynaptic currents (EPSC) of CA3 interneurones evoked by the mossy fibres (MF) or commissural/associational (C/A) axons, show input-specific synaptic potentiation in response to TrkB stimulation. On CA3 pyramidal cells, stimulation with DHF potentiates the MF synaptic transmission and increases the MF-EPSP - spike coupling. The latter exhibits a dramatic increase when picrotoxin is bath perfused after DHF, indicating that local interneurones restrain the excitability mediated by activation of TrkB. Therefore, we propose that release of BDNF on area CA3 reshapes the output of this hippocampal region by simultaneous activation of TrkB on GABAergic interneurones and pyramidal cells.

摘要

哺乳动物大脑的齿状回和海马 CA3 区含有最高水平的脑源性神经营养因子 (BDNF) 和其经典膜受体原肌球蛋白相关激酶 B (TrkB)。因此,本研究检查了激活 TrkB 后对大鼠海马 CA3 区内神经元和锥体神经元引发的表达和生理反应。TrkB、谷氨酸脱羧酶 67 和钙结合蛋白 parvalbumin、calbindin 或 calretinin 的三重免疫标记证实了 TrkB 在所有 CA3 亚层中的体细胞表达。具有快速放电的 TrkB 阳性中间神经元仅限于层或 lucidum,而规则放电的中间神经元存在于层 lucidum、放射状和腔隙状分子层。用 7,8-二羟基黄酮 (DHF) 激活 TrkB 受体调节从 CA3 中间神经元记录的自发突触电流的幅度和频率。此外,苔藓纤维 (MF) 或连合/关联 (C/A) 轴突诱发的 CA3 中间神经元的分离兴奋性突触后电流 (EPSC) 显示出对 TrkB 刺激的输入特异性突触增强。在 CA3 锥体神经元上,用 DHF 刺激可增强 MF 突触传递,并增加 MF-EPSP - 尖峰耦合。当 DHF 后用 picrotoxin 灌流时,后者会急剧增加,表明局部中间神经元抑制了由激活 TrkB 介导的兴奋性。因此,我们提出 BDNF 在 CA3 区的释放通过同时激活 GABA 能中间神经元和锥体神经元上的 TrkB 来重塑该海马区域的输出。

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