韁核habenula,拉丁語中habena表示韁繩)是位於脊椎動物丘腦背側的一個體積較小的雙側核團,其體積小於一粒豌豆,形狀細長。其與第三腦室接壤,位於松果體前面。[1]

韁核
韁核(紅色)位於松果體或丘腦前面的位置。
如圖,韁核(藍色)位於松果體(紅色)前面。
標識字符
MeSHD019262
NeuroNames英語NeuroNames294
NeuroLex英語NeuroLex IDbirnlex_1611
TA98A14.1.08.003
TA25662
FMAFMA:62032
神經解剖學術語英語Anatomical terms of neuroanatomy

儘管韁核十分微小,但每個韁核都分為兩個不同的區域:內側韁核 (MHb) 和外側韁核 (LHb),兩者都具有不同的神經元群、傳入纖維和傳出纖維。[2][3] 內側韁核可以再分為五個亞核,而外側韁核則可分為四個亞核。[4]研究顯示內側韁核及外側韁核形態的複雜性,內側韁核不同的傳入纖維分別投射到不同的亞核。[5]內外側韁核之間不同的基因表現使兩個區域有不同的功能。[6]

韁核是脊椎動物演化中的保守結構,哺乳動物的韁核是高度對稱的,而魚類兩棲類爬蟲類的韁核在大小、分子組成及連接方面都極不對稱。[1]韁核是邊緣系統通路中一個主要組成部分,[1]韁核和腳間核英語interpeduncular nucleus之間的後屈束英語fasciculus retroflexus路徑是發育中的大腦中首先形成的主要神經束之一。[1]

韁核是連接前腦區域和中腦區域的中央結構,為情緒和感覺處理整合的樞紐或交點,[2]它整合來自邊緣系統、感官和基底核的訊息來做出適當且有效的反應措施。[5]韁核參與單胺神經傳導物質的調節,特別是多巴胺和血清素,[2][3]這兩種神經傳導物質都與焦慮症和迴避行為密切相關。[2]韁核的功能也涉及動機、情緒、學習以及痛覺[2]內側韁核在憂鬱、壓力、記憶和尼古丁戒斷中發揮重要作用,也在可卡因、安非他命和酒精成癮中發揮重要作用。[6]內側韁核表現出高水平的煙鹼型乙酰膽鹼受體 (nAChR),其參與多種形式的成癮。[6]

解剖學

編輯

每個韁核都分為內側及外側兩個部分,研究顯示內側韁核可以再分為五個亞核,而外側韁核則可分為四個亞核。[4] 左右韁核由韁連合相連接,松果體附着於腦部此區域。[7]

外側韁核

編輯

外側韁核主要的傳入區域是外側視前區英語preoptic area、腹側蒼白球英語pallidum、外側下丘腦、內側韁核和蒼白球的內部。[8]外側韁核中的神經元是「負向獎勵」的,因為它們會被與不愉快事件、獎賞的缺乏或懲罰的存在相關的刺激活化。[9] 外側韁核的獎勵訊息來自蒼白球內部。[10]

外側韁核的輸出作用於多巴胺能區域、血清素區域及膽鹼能區域[8]此輸出抑制黑質緻密部和腹側被蓋區的多巴胺神經元,外側韁核的活化與其失去活性相關,相反的,外側韁核的失活也與其活化相關。[11]外側韁核的功能是抵抗外側被蓋核在獲得迴避反應時的作用,但在形成記憶、動機或執行時,不會對迴避反應起作用。[12] 研究表明,外側韁核可能在決策中發揮至關重要的作用,[13]研究也表明,外側韁核活性異常和憂鬱症之間存在關聯。[14]

內側韁核

編輯

內側韁核接收來自後部透明中隔英語septum pellucidumBroca氏對角帶英語diagonal band of Broca,外側韁核接收來自外側下丘腦伏隔核、蒼白球內側部、腹側蒼白球和Broca氏對角帶的傳入訊號。[8] 整體而言,這個複雜互連的區域是背側間腦傳導系統英語dorsal diencephalic conduction system(DDCS)的一部分,負責將訊息從邊緣系統傳遞到中腦後腦內側前腦[15][16]

內側韁核的輸入來自各個區域並攜帶許多不同的化學物質。傳入區域包括間隔核英語septal nuclei、來自腹側被蓋區束間核的多巴胺能輸入,來自藍斑核的去甲腎上腺素能輸入以及來自Broca對角帶的GABA能輸入。內側韁核將麩胺酸P物質乙酰膽鹼的輸出通過腳間核發送到導水管周圍灰質以及松果體。[17][18]

不對稱性

編輯

Nikolaus Goronowitsch[7]在1883年發現了韁核的不對稱性,許多物種皆展現了韁核神經元左右不對稱的分化。[7]在許多魚類兩棲動物中,一側的韁核明顯比另一側大,並且更好地組織成背側間腦中的不同核。這種分化的側面(無論是左側較發達還是右側較發達)因物種而異。而鳥類哺乳類的兩個韁核都比較對稱,並且每側都由內側核和外側核組成,在魚類和兩棲動物中分別相當於背側韁核和腹側韁核。[19][8][20]

嗅覺編碼

編輯

在一些魚(七鰓鰻硬骨魚)中,僧帽細胞英語mitral cell(主要嗅覺神經元)軸突以不對稱的方式專門投射到韁核的右半球,這表示背側韁核在功能上不對稱,主要是右半球的氣味反應。 研究還表明,即使沒有嗅覺刺激,背側韁核神經元也會自發性活躍。 這些自發性活動的背側韁核神經元被組織成功能簇,旨在控制嗅覺反應。

功能

編輯

這個核團被認為參與單胺類神經傳導物質,如多巴胺血清素的調節。[21][22]

韁核參與疼痛處理、生殖行為、營養、睡眠-覺醒週期、壓力反應和學習。近期使用功能性磁振造影[23]和單一單元電生理學[11]的演示將外側韁核的功能與獎勵處理緊密聯繫起來,特別是在編碼負回饋或負獎勵方面。Matsumoto(松本)和Hikosaka(彥坂)在2007年提出,大腦中的獎勵和負面獎勵信息可能通過外側韁核、基底神經節和單胺能(多巴胺和血清素)系統之間的相互作用加以詳細說明,並且外側韁核可能在這種整合功能中發揮關鍵作用。[11] 其後Bromberg-Martin等人於2011年強調,除了正向和負向獎勵預測錯誤之外,外側韁核中的神經元還發出正向和負向資訊預測錯誤訊號。[24]

與憂鬱症的關聯

編輯

患有重度憂鬱症的患者,內側和外側韁核的體積均減少,右側神經元細胞數量也減少,[25]這種變化在精神分裂症患者中不會出現。[25]外側韁核的主要傳入束(即丘腦髓紋)的深部腦刺激已被用於治療嚴重、遷延且難以治療的憂鬱症。[26][27]

在動物研究中,外側韁核的NMDA受體依賴性爆發與憂鬱症有關,[28]並且已經證明,全身麻醉劑氯胺酮能當作受體拮抗劑來阻止這種放電。[29]氯胺酮在人類中顯示出快速作用的抗憂鬱作用(劑量為0.5毫克/體重/公斤)後,已成為許多研究的主題。[30]

動機和成癮

編輯

近期對韁核的研究已經開始將結構與有機體當前的情緒、動機感和獎勵識別聯繫起來。[31] 外側韁核原先被認為是一種「反獎勵」訊號,但後來的研究表明外側韁核有助於識別偏好、幫助大腦區分潛在的行動和隨後的動機決策。[32] 在一項使用巴甫洛夫條件反射模型的研究中,結果顯示韁核反應增加,[33] 這種增加與懲罰(即電擊)相關的條件刺激同時發生。[33] 因此,研究人員推測,若外側韁核的抑制或損傷導致無法處理此類訊息,則可能導致隨機動機行為。[32][33]外側韁核對於理解獎勵和動機關係尤其重要,因為它與成癮行為有關,[31] 其抑制多巴胺能神經元,減少多巴胺的釋放。[34] 多項動物研究表明,接受獎勵與多巴胺濃度升高同時發生,但一旦動物學會了習得關聯,多巴胺濃度就會保持升高,只有在獎勵被取消時才會降低。[20][22][31][34] 因此,多巴胺濃度只會隨着不可預測的獎勵和「正預測錯誤」而增加。[20]此外,去除預期獎勵會活化外側韁核,抑制多巴胺濃度,[20]這項發現解釋了為什麼成癮藥物與多巴胺濃度升高有關。[20]

尼古丁與煙鹼型乙酰膽鹼受體

編輯

根據國家藥物濫用研究所英語National Institute on Drug Abuse的數據,美國五分之一的可預防的死亡是由煙草的使用引起的。[35]尼古丁是大多數煙草製品中發現的成癮藥物,很容易被身體的血液吸收。[35] 儘管人們容易誤解使用煙草和尼古丁具有放鬆作用,但動物行為測試顯示尼古丁具有致焦慮作用。[36] 煙鹼型乙酰膽鹼受體(nAChR)已被確定為尼古丁活性的主要位點並調節隨後的細胞極化。[37]煙鹼型乙酰膽鹼受體由許多α和β亞基組成,在外側韁核及內側韁核中都有發現,研究表明它們可能在成癮和戒斷行為中發揮關鍵作用。[37][38]

歷史

編輯

韁核是一種在3.6億多年前出現在脊椎動物中的保守結構,[4]安德烈亞斯·維薩留斯於1555年首次描述了韁連合,[39]狄奧多·赫曼·梅涅特則在1872年提到了韁核。[40]

參考來源

編輯
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外部連結

編輯


  • 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 .