Nguyen Peter V, Gelinas Jennifer N
a Department of Physiology and Institute of Neuroscience & Mental Health , University of Alberta School of Medicine , Edmonton , Canada.
b Department of Neurology and Institute for Genomic Medicine , College of Physicians & Surgeons of Columbia University , New York , NY , USA.
J Neurogenet. 2018 Sep;32(3):171-182. doi: 10.1080/01677063.2018.1497630. Epub 2018 Sep 3.
Altered synaptic strength underlies information storage in neural circuits. Neuromodulatory transmitters such as norepinephrine (NE) facilitate long-lasting synaptic plasticity by recruiting and modifying multiple molecular elements of synaptic signaling, including specific transmitter receptors, intracellular protein kinases, and translation initiation. NE regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors (β-ARs), which bind NE and are critical for gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in neural circuits. In this article, in honor of Prof. Harold Atwood, we review the contributions of β-ARs towards gating the expression of protein synthesis-dependent, long-lasting hippocampal LTP. We focus on the roles of β-ARs in modifying ion channels, glutamatergic AMPA receptors, and translation initiation factors during LTP. We discuss prospective research strategies that may lead to increased understanding of the roles of NE in regulating neural circuit physiology; these may uncover novel therapies for treatment of specific neurological disorders linked to aberrant circuit activity and dysfunctional noradrenergic synaptic transmission.
突触强度的改变是神经回路中信息存储的基础。去甲肾上腺素（NE）等神经调质通过募集和修饰突触信号传导的多种分子元件，包括特定的递质受体、细胞内蛋白激酶和翻译起始，促进持久的突触可塑性。NE调节多种脑功能，如注意力、感知、觉醒、睡眠、学习和记忆。哺乳动物海马体接受去甲肾上腺素能神经支配，海马神经元表达β-肾上腺素能受体（β-ARs），其与NE结合，对于控制持久形式的突触增强的诱导至关重要。这些形式的长期增强（LTP）被认为对神经回路中空间和情境记忆的长期存储有重要贡献。在本文中，为纪念哈罗德·阿特伍德教授，我们综述了β-ARs在控制蛋白质合成依赖性、持久的海马体LTP表达方面的贡献。我们重点关注β-ARs在LTP期间修饰离子通道、谷氨酸能AMPA受体和翻译起始因子中的作用。我们讨论了可能有助于增加对NE在调节神经回路生理学中作用理解的前瞻性研究策略；这些策略可能揭示治疗与异常回路活动和功能失调的去甲肾上腺素能突触传递相关的特定神经疾病的新疗法。
