Ultrastructural Localization of Full-Length trkB Immunoreactivity in Rat Hippocampus Suggests Multiple Roles in Modulating Activity-Dependent Synaptic Plasticity
Ultrastructural Localization of Full-Length trkB Immunoreactivity in Rat Hippocampus Suggests Multiple Roles in Modulating Activity-Dependent Synaptic Plasticity
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DOI：
10.1523/jneurosci.19-18-08009.1999
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发表时间：
1999-09
期刊：
影响因子：
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通讯作者：
C. Drake;T. Milner;S. Patterson
中科院分区：
文献类型：
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作者：
C. Drake;T. Milner;S. Patterson
作用于 trkB 受体的神经营养素已被证明是海马活动依赖性可塑性的重要调节剂，但这些作用背后的机制尚不清楚。为了确定成年大鼠海马结构中 trkB 配体的细胞和亚细胞靶标，使用电子显微镜定位全长 trkB 受体免疫反应性 (trkB-IR)。 trkB-IR 存在于谷氨酸能锥体细胞和颗粒细胞中。这些神经元中的标记表现为离散的簇，主要存在于轴突、兴奋型轴突末端和树突棘中，少量存在于体细胞和树突轴中。 trkB-IR 通常在树突棘的质膜上发现，而在其他亚细胞区域，trkB-IR 通常在细胞内。轴突初始片段内的标记非常密集，表明存在广泛的受体贩运。 trkB-IR 不限于锥体细胞和颗粒细胞。偶尔在中间神经元轴突初始片段中发现密集的 trkB-IR，一些轴突末端在体细胞和树突轴上形成抑制型突触，而兴奋型末端可能起源于海马外。这表明 trkB 包含在一些 GABA 能中间神经元、神经调节（例如胆碱能、多巴胺能和去甲肾上腺素能）传入神经和/或谷氨酸能传入神经中。这些数据表明，全长 trkB 受体激活可以调节三突触回路的谷氨酸能通路，既可以调节突触前的轴突末端和起始段，也可以调节突触后的树突棘和轴。通过催化 trkB 发出的信号也可能对突触前影响抑制性和调节性神经元。泛 trkB 抗体标记的神经元群与全长特异性 trkB 抗血清相同，但不同亚细胞位点的标记密度不同。这些发现为进一步研究作用于 trkB 受体的神经营养因子促进突触可塑性的机制提供了超微结构基础。
Neurotrophins acting at the trkB receptor have been shown to be important modulators of activity-dependent plasticity in the hippocampus, but the mechanisms underlying these effects are not yet well understood. To identify the cellular and subcellular targets of trkB ligands in the adult rat hippocampal formation, full-length trkB receptor immunoreactivity (trkB-IR) was localized using electron microscopy. trkB-IR was present in the glutamatergic pyramidal and granule cells. Labeling in these neurons appeared as discrete clusters and was primarily in axons, excitatory-type axon terminals, and dendritic spines and to a lesser extent in somata and dendritic shafts. trkB-IR was commonly found on the plasma membrane of dendritic spines, whereas in other subcellular regions trkB-IR was often intracellular. Labeling was strikingly dense within axon initial segments, suggesting extensive receptor trafficking. trkB-IR was not confined to pyramidal and granule cells. Dense trkB-IR was found in occasional interneuron axon initial segments, some axon terminals forming inhibitory-type synapses onto somata and dendritic shafts, and excitatory-type terminals likely to originate extrahippocampally. This suggests that trkB is contained in some GABAergic interneurons, neuromodulatory (e.g., cholinergic, dopaminergic, and noradrenergic) afferents, and/or glutamatergic afferents. These data indicate that full-length trkB receptor activation may modulate glutamatergic pathways of the trisynaptic circuit both presynaptically at axon terminals and initial segments and postsynaptically at dendritic spines and shafts. Signaling via catalytic trkB may also presynaptically affect inhibitory and modulatory neurons. A pan-trkB antibody labeled the same neuronal populations as the full-length-specific trkB antiserum, but the labels differed in density at various subcellular sites. These findings provide an ultrastructural foundation for further examining the mechanisms through which neurotrophins acting at trkB receptors contribute to synaptic plasticity.