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缰核

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缰核
缰核(红色)位于松果体或丘脑前面的位置。
如图,缰核(蓝色)位于松果体(红色)前面。
标识字符
MeSHD019262
NeuroNames英语NeuroNames294
NeuroLex英语NeuroLex IDbirnlex_1611
TA98A14.1.08.003
TA25662
FMAFMA:62032
神经解剖学术语英语Anatomical terms of neuroanatomy

缰核habenula,拉丁语中habena表示缰绳)是位于脊椎动物丘脑背侧的一个体积较小的双侧核团,其体积小于一粒豌豆,形状细长。其与第三脑室接壤,位于松果体前面。[1]

尽管缰核十分微小,但每个缰核都分为两个不同的区域:内侧缰核 (MHb) 和外侧缰核 (LHb),两者都具有不同的神经元群、传入纤维和传出纤维。[2][3] 内侧缰核可以再分为五个亚核,而外侧缰核则可分为四个亚核。[4]研究显示内侧缰核及外侧缰核形态的复杂性,内侧缰核不同的传入纤维分别投射到不同的亚核。[5]内外侧缰核之间不同的基因表现使两个区域有不同的功能。[6]

缰核是脊椎动物演化中的保守结构,哺乳动物的缰核是高度对称的,而鱼类两栖类爬虫类的缰核在大小、分子组成及连接方面都极不对称。[1]缰核是边缘系统通路中一个主要组成部分,[1]缰核和脚间核英语interpeduncular nucleus之间的后屈束英语fasciculus retroflexus路径是发育中的大脑中首先形成的主要神经束之一。[1]

缰核是连接前脑区域和中脑区域的中央结构,为情绪和感觉处理整合的枢纽或交点,[2]它整合来自边缘系统、感官和基底核的讯息来做出适当且有效的反应措施。[5]缰核参与单胺神经传导物质的调节,特别是多巴胺和血清素,[2][3]这两种神经传导物质都与焦虑症和回避行为密切相关。[2]缰核的功能也涉及动机、情绪、学习以及痛觉[2]内侧缰核在忧郁、压力、记忆和尼古丁戒断中发挥重要作用,也在古柯碱、安非他命和酒精成瘾中发挥重要作用。[6]内侧缰核表现出高水平的烟碱型乙酰胆碱受体 (nAChR),其参与多种形式的成瘾。[6]

解剖学

每个缰核都分为内侧及外侧两个部分,研究显示内侧缰核可以再分为五个亚核,而外侧缰核则可分为四个亚核。[4] 左右缰核由缰连合相连接,松果体附着于脑部此区域。[7]

外侧缰核

外侧缰核主要的传入区域是外侧视前区英语preoptic area、腹侧苍白球英语pallidum、外侧下丘脑、内侧缰核和苍白球的内部。[8]外侧缰核中的神经元是“负向奖励”的,因为它们会被与不愉快事件、奖赏的缺乏或惩罚的存在相关的刺激活化。[9] 外侧缰核的奖励讯息来自苍白球内部。[10]

外侧缰核的输出作用于多巴胺能区域、血清素区域及胆碱能区域[8]此输出抑制黑质致密部和腹侧被盖区的多巴胺神经元,外侧缰核的活化与其失去活性相关,相反的,外侧缰核的失活也与其活化相关。[11]外侧缰核的功能是抵抗外侧被盖核在获得回避反应时的作用,但在形成记忆、动机或执行时,不会对回避反应起作用。[12] 研究表明,外侧缰核可能在决策中发挥至关重要的作用,[13]研究也表明,外侧缰核活性异常和忧郁症之间存在关联。[14]

内侧缰核

内侧缰核接收来自后部透明中隔英语septum pellucidumBroca氏对角带英语diagonal band of Broca,外侧缰核接收来自外侧下丘脑伏隔核、苍白球内侧部、腹侧苍白球和Broca氏对角带的传入讯号。[8] 整体而言,这个复杂互连的区域是背侧间脑传导系统英语dorsal diencephalic conduction system(DDCS)的一部分,负责将讯息从边缘系统传递到中脑后脑内侧前脑[15][16]

内侧缰核的输入来自各个区域并携带许多不同的化学物质。传入区域包括间隔核英语septal nuclei、来自腹侧被盖区束间核的多巴胺能输入,来自蓝斑核的去甲肾上腺素能输入以及来自Broca对角带的GABA能输入。内侧缰核将麸胺酸P物质乙酰胆碱的输出通过脚间核发送到导水管周围灰质以及松果体。[17][18]

不对称性

Nikolaus Goronowitsch[7]在1883年发现了缰核的不对称性,许多物种皆展现了缰核神经元左右不对称的分化。[7]在许多鱼类两栖动物中,一侧的缰核明显比另一侧大,并且更好地组织成背侧间脑中的不同核。这种分化的侧面(无论是左侧较发达还是右侧较发达)因物种而异。而鸟类哺乳类的两个缰核都比较对称,并且每侧都由内侧核和外侧核组成,在鱼类和两栖动物中分别相当于背侧缰核和腹侧缰核。[19][8][20]

嗅觉编码

在一些鱼(七鳃鳗硬骨鱼)中,僧帽细胞英语mitral cell(主要嗅觉神经元)轴突以不对称的方式专门投射到缰核的右半球,这表示背侧缰核在功能上不对称,主要是右半球的气味反应。 研究还表明,即使没有嗅觉刺激,背侧缰核神经元也会自发性活跃。 这些自发性活动的背侧缰核神经元被组织成功能簇,旨在控制嗅觉反应。

功能

这个核团被认为参与单胺类神经传导物质,如多巴胺血清素的调节。[21][22]

缰核参与疼痛处理、生殖行为、营养、睡眠-觉醒周期、压力反应和学习。近期使用功能性磁振造影[23]和单一单元电生理学[11]的演示将外侧缰核的功能与奖励处理紧密联系起来,特别是在编码负回馈或负奖励方面。Matsumoto(松本)和Hikosaka(彦坂)在2007年提出,大脑中的奖励和负面奖励信息可能通过外侧缰核、基底神经节和单胺能(多巴胺和血清素)系统之间的相互作用加以详细说明,并且外侧缰核可能在这种整合功能中发挥关键作用。[11] 其后Bromberg-Martin等人于2011年强调,除了正向和负向奖励预测错误之外,外侧缰核中的神经元还发出正向和负向资讯预测错误讯号。[24]

与忧郁症的关联

患有重度忧郁症的患者,内侧和外侧缰核的体积均减少,右侧神经元细胞数量也减少,[25]这种变化在精神分裂症患者中不会出现。[25]外侧缰核的主要传入束(即丘脑髓纹)的深部脑刺激已被用于治疗严重、迁延且难以治疗的忧郁症。[26][27]

在动物研究中,外侧缰核的NMDA受体依赖性爆发与忧郁症有关,[28]并且已经证明,全身麻醉剂氯胺酮能当作受体拮抗剂来阻止这种放电。[29]氯胺酮在人类中显示出快速作用的抗忧郁作用(剂量为0.5毫克/体重/公斤)后,已成为许多研究的主题。[30]

动机和成瘾

近期对缰核的研究已经开始将结构与有机体当前的情绪、动机感和奖励识别联系起来。[31] 外侧缰核原先被认为是一种“反奖励”讯号,但后来的研究表明外侧缰核有助于识别偏好、帮助大脑区分潜在的行动和随后的动机决策。[32] 在一项使用巴甫洛夫条件反射模型的研究中,结果显示缰核反应增加,[33] 这种增加与惩罚(即电击)相关的条件刺激同时发生。[33] 因此,研究人员推测,若外侧缰核的抑制或损伤导致无法处理此类讯息,则可能导致随机动机行为。[32][33]外侧缰核对于理解奖励和动机关系尤其重要,因为它与成瘾行为有关,[31] 其抑制多巴胺能神经元,减少多巴胺的释放。[34] 多项动物研究表明,接受奖励与多巴胺浓度升高同时发生,但一旦动物学会了习得关联,多巴胺浓度就会保持升高,只有在奖励被取消时才会降低。[20][22][31][34] 因此,多巴胺浓度只会随着不可预测的奖励和“正预测错误”而增加。[20]此外,去除预期奖励会活化外侧缰核,抑制多巴胺浓度,[20]这项发现解释了为什么成瘾药物与多巴胺浓度升高有关。[20]

尼古丁与烟碱型乙酰胆碱受体

根据国家药物滥用研究所英语National Institute on Drug Abuse的数据,美国五分之一的可预防的死亡是由烟草的使用引起的。[35]尼古丁是大多数烟草制品中发现的成瘾药物,很容易被身体的血液吸收。[35] 尽管人们容易误解使用烟草和尼古丁具有放松作用,但动物行为测试显示尼古丁具有致焦虑作用。[36] 烟碱型乙酰胆碱受体(nAChR)已被确定为尼古丁活性的主要位点并调节随后的细胞极化。[37]烟碱型乙酰胆碱受体由许多α和β亚基组成,在外侧缰核及内侧缰核中都有发现,研究表明它们可能在成瘾和戒断行为中发挥关键作用。[37][38]

历史

缰核是一种在3.6亿多年前出现在脊椎动物中的保守结构,[4]安德烈亚斯·维萨留斯于1555年首次描述了缰连合,[39]狄奥多·赫曼·梅涅特则在1872年提到了缰核。[40]

参考来源

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外部链接


  • Jetti SK, Vendrell-Llopis N, Yaksi E. Spontaneous activity governs olfactory representations in spatially organized habenular microcircuits. Current Biology. February 2014, 24 (4): 434–9. PMID 24508164. doi:10.1016/j.cub.2014.01.015可免费查阅.