Drake C T, Milner T A, Patterson S L
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York, New York 10021, USA.
J Neurosci. 1999 Sep 15;19(18):8009-26. doi: 10.1523/JNEUROSCI.19-18-08009.1999.
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.
作用于trkB受体的神经营养因子已被证明是海马体中与活动相关可塑性的重要调节因子，但其作用机制尚未完全清楚。为了确定成年大鼠海马结构中trkB配体的细胞和亚细胞靶点，利用电子显微镜对全长trkB受体免疫反应性（trkB-IR）进行了定位。trkB-IR存在于谷氨酸能锥体神经元和颗粒细胞中。这些神经元中的标记呈现为离散的簇状，主要位于轴突、兴奋性轴突终末和树突棘，在胞体和树突干中较少。trkB-IR常见于树突棘的质膜上，而在其他亚细胞区域，trkB-IR通常位于细胞内。轴突起始段的标记非常密集，表明存在广泛的受体运输。trkB-IR并不局限于锥体神经元和颗粒细胞。在偶尔的中间神经元轴突起始段、一些在胞体和树突干上形成抑制性突触的轴突终末以及可能起源于海马体外的兴奋性终末中发现了密集的trkB-IR。这表明trkB存在于一些γ-氨基丁酸能中间神经元、神经调节（如胆碱能、多巴胺能和去甲肾上腺素能）传入纤维和/或谷氨酸能传入纤维中。这些数据表明，全长trkB受体的激活可能在轴突终末和起始段的突触前以及树突棘和树突干的突触后调节三突触回路的谷氨酸能通路。通过催化性trkB的信号传导也可能在突触前影响抑制性和调节性神经元。一种泛trkB抗体标记的神经元群体与全长特异性trkB抗血清相同，但在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。
