Aumann Tim D
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
J Chem Neuroanat. 2016 Apr;73:21-32. doi: 10.1016/j.jchemneu.2015.12.009. Epub 2015 Dec 21.
The ability of neurons to change the amount or type of neurotransmitter they use, or 'neurotransmitter plasticity', is an emerging new form of adult brain plasticity. For example, it has recently been shown that neurons in the adult rat hypothalamus up- or down-regulate dopamine (DA) neurotransmission in response to the amount of light the animal receives (photoperiod), and that this in turn affects anxiety- and depressive-like behaviors (Dulcis et al., 2013). In this Chapter I consolidate recent evidence from my laboratory suggesting neurons in the adult mouse substantia nigra pars compacta (SNc) also undergo DA neurotransmitter plasticity in response to persistent changes in their electrical activity, including that driven by the mouse's environment or behavior. Specifically, we have shown that the amounts of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) gene promoter activity, TH mRNA and TH protein in SNc neurons increases or decreases after ∼20h of altered electrical activity. Also, infusion of ion-channel agonists or antagonists into the midbrain for 2 weeks results in ∼10% (∼500 neurons) more or fewer TH immunoreactive (TH+) SNc neurons, with no change in the total number of SNc neurons (TH+ and TH-). Targeting ion-channels mediating cell-autonomous pacemaker activity in, or synaptic input and afferent pathways to, SNc neurons are equally effective in this regard. In addition, exposing mice to different environments (sex pairing or environment enrichment) for 1-2 weeks induces ∼10% more or fewer TH+ SNc (and ventral tegmental area or VTA) neurons and this is abolished by concurrent blockade of synaptic transmission in midbrain. Although further research is required to establish SNc (and VTA) DA neurotransmitter plasticity, and to determine whether it alters brain function and behavior, it is an exciting prospect because: (1) It may play important roles in movement, motor learning, reward, motivation, memory and cognition; and (2) Imbalances in midbrain DA cause symptoms associated with several prominent brain and behavioral disorders such as schizophrenia, addiction, obsessive-compulsive disorder, depression, Parkinson's disease and attention-deficit and hyperactivity disorder. Midbrain DA neurotransmitter plasticity may therefore play a role in the etiology of these symptoms, and might also offer new treatment options.
神经元改变其使用的神经递质的数量或类型的能力，即“神经递质可塑性”，是成人大脑可塑性中一种新出现的形式。例如，最近有研究表明，成年大鼠下丘脑的神经元会根据动物接收到的光照量（光周期）上调或下调多巴胺（DA）神经传递，而这反过来又会影响焦虑样和抑郁样行为（杜尔西斯等人，2013年）。在本章中，我整合了我实验室最近的证据，表明成年小鼠黑质致密部（SNc）的神经元也会因电活动的持续变化而发生DA神经递质可塑性，包括由小鼠的环境或行为驱动的变化。具体而言，我们已经表明，在电活动改变约20小时后，SNc神经元中酪氨酸羟化酶（TH，DA合成中的限速酶）基因启动子活性、TH mRNA和TH蛋白的量会增加或减少。此外，向中脑注射离子通道激动剂或拮抗剂2周会导致TH免疫反应性（TH+）SNc神经元数量增加或减少约10%（约500个神经元），而SNc神经元的总数（TH+和TH-）没有变化。在这方面，靶向介导SNc神经元自主起搏器活动的离子通道，或其突触输入和传入通路同样有效。此外，将小鼠置于不同环境（性别配对或环境富集）中1 - 2周会使TH+ SNc（以及腹侧被盖区或VTA）神经元数量增加或减少约10%，而中脑突触传递的同时阻断会消除这种变化。尽管需要进一步研究来确定SNc（和VTA）的DA神经递质可塑性，并确定它是否会改变脑功能和行为，但这是一个令人兴奋的前景，因为：（1）它可能在运动、运动学习、奖赏、动机、记忆和认知中发挥重要作用；（2）中脑DA失衡会导致与几种主要脑和行为障碍相关的症状，如精神分裂症、成瘾、强迫症、抑郁症、帕金森病以及注意力缺陷多动障碍。因此，中脑DA神经递质可塑性可能在这些症状的病因中起作用，并可能提供新的治疗选择。
