Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors.
Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors.
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DOI：
10.1042/ns20180066
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发表时间：
2019-03-01
影响因子：
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通讯作者：
Coulson, Elizabeth J
中科院分区：
文献类型：
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作者：
Boskovic, Zoran;Meier, Sonja;Coulson, Elizabeth J
胆碱能基底前脑（cBF）神经元除胆碱能标志物外，还表达p75神经营养因子受体（p75NTR）和原肌球蛋白相关激酶（Trk）神经营养因子受体。已知神经营养因子，特别是神经生长因子（NGF），介导胆碱能神经元的发育和维持。然而，神经营养因子信号传导在调节成人cBF功能中的作用尚不清楚，尽管在痴呆症中，营养信号传导减少，p75NTR介导cBF神经元的神经变性。在这里，我们回顾了目前对cBF神经元如何被激活p75NTR和TrkA， B或C的神经营养因子调节的理解，以影响这些神经元在正常皮层功能，特别是高阶认知中发挥的关键作用。具体来说，我们描述了神经营养因子调节基底前脑神经元的发育及其在维持和修改成熟基底前脑突触和皮层微回路连接中的作用的现有证据。了解神经营养因子信号在调节胆碱能连接的准确性方面所起的作用，将有助于理解正常的认知过程，并可能为设计改善治疗胆碱能功能障碍的神经系统疾病的治疗方法提供额外的想法。
Cholinergic basal forebrain (cBF) neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase (Trk) neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor (NGF), mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling in regulating adult cBF function is less clear, although in dementia, trophic signalling is reduced and p75NTR mediates neurodegeneration of cBF neurons. Here we review the current understanding of how cBF neurons are regulated by neurotrophins which activate p75NTR and TrkA, B or C to influence the critical role that these neurons play in normal cortical function, particularly higher order cognition. Specifically, we describe the current evidence that neurotrophins regulate the development of basal forebrain neurons and their role in maintaining and modifying mature basal forebrain synaptic and cortical microcircuit connectivity. Understanding the role neurotrophin signalling plays in regulating the precision of cholinergic connectivity will contribute to the understanding of normal cognitive processes and will likely provide additional ideas for designing improved therapies for the treatment of neurological disease in which cholinergic dysfunction has been demonstrated.