終紋床核在記憶穩固歷程中的角色─麩胺酸雨正腎上腺素之互動

Role of the Bed Nucleus of the Stria Terminalis on Memory Formation Precesses: Interaction Between Norepinephrine and Glutamate

劉姿蘭(Tzu-Lan Liu)

指導教授 ： 梁庚辰

國立臺灣大學/理學院/心理學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.00994

摘要

許多研究指出，情緒記憶的形成涉及杏仁核內的神經機制與其輸入、輸出結構的神經互動。終紋床核（bed nucleus of the stria terminalis）是杏仁核一重要的聯絡區域，它透過終紋（stria terminalis）與杏仁核進行溝通。過去的研究顯示，終紋床核上分佈有正腎上腺素與麩胺酸神經，且彼此間會相互影響。過去甚少研究探討終紋床核內正腎上腺素與麩胺酸在學習記憶上所扮演的角色。因此本論文利用抑制型逃避作業、水迷津作業與驚跳反應之恐懼增益作業探討終紋床核內麩胺酸NMDA（N-methyl-D-aspartic acid）受器在記憶穩固歷程中的角色，並進一步探討該受器與正腎上腺素之互動。實驗1發現訓練後在終紋床核內注射麩胺酸會促進大白鼠在抑制型逃避作業的記憶表現，且此效果可被APV（DL-2-amino-5-phosphonovaleric acid）逆轉。實驗2發現訓練後以APV阻斷終紋床核內NMDA受器會損害大白鼠在抑制型逃避作業的記憶表現。然而麩胺酸與APV不影響動物在水迷津作業與驚跳反應之恐懼增益作業上的記憶表現。實驗3發現麩胺酸與正腎上腺素對促進抑制型逃避記憶具有加成效果（additive effect）。實驗4顯示APV對記憶的損害效果可被正腎上腺素逆轉。實驗5發現麩胺酸對記憶的促進效果無法被α1受器拮抗劑prazosin減弱。實驗6於訓練後以propranolol阻斷終紋床核內β受器會損害大白鼠在抑制型逃避作業的記憶表現，而正腎上腺素對記憶的促進效果可以被propranolol逆轉。實驗7顯示麩胺酸對記憶的促進效果可被β受器拮抗劑propranolol逆轉。綜合以上之結果，終紋床核內NMDA受器與β受器參與抑制型逃避記憶的穩固，而麩胺酸與正腎上腺素可以分別透過NMDA受器與β受器調節抑制型逃避記憶的穩固。另外，經NMDA受器調節釋放的正腎上腺素會透過β受器參與抑制型逃避記憶的穩固歷程。這些結果顯示終紋床核在逃避記憶的形成上扮演重要角色。

關鍵字

NMDA受器 ； β受器 ； 正腎上腺素 ； 終紋床核 ； 麩胺酸 ； 逃避學習

並列摘要

Extensive evidence implicates the amygdala in modulation of memory processes. Previous research indicated that the stria terminalis mediates the memory modulatory influences from the amygdala. The bed nucleus of the stria terminalis (BNST) is a projection target of the stria terminalis. Neuroanatomical and immunohistochemical studies demonstrated a variety of neurotransmitters and neuropeptides, including norepinephrine and glutamate, present in the perikarya or afferent terminals of the BNST. Some of the noradrenergic terminals in the BNST possess presynaptic NMDA receptors. Norephinephrine released in the BNST may be regulated by presynaptic NMDA receptors. Moreover, previous evidence showed that norepinephrine released in the BNST could modulate memory processes through ?-adrenergic receptors. While the NMDA receptor in various brain regions is importanted in neural plasticity, but its role in the BNST in terms of interacting with norepinephrine in modulating memory processing is still obscured. The present study investigated the involvement of NMDA receptors, as well as the interaction of norepinephrine and glutamate in the BNST in memory consolidation processes. Rats with the BNST bilaterally implanted cannula were trained on the inhibitory avoidance task, water maze task, and fear-potentiated startle task. Drugs were bilaterally infused into the BNST shortly after training. Results indicated that immediate post-training intra-BNST infusion of 1.0 μg L-glutamate enhanced retention of the inhibitory avoidance response, and the memory enhancing effect was attenuated by 1.0 μg APV. Post-training intra-BNST infusion of 5.0 μg APV impaired retention of the inhibitory avoidance task. These effects were not observed in either the water maze or the fear-potentiated startle task. Posttraining intra-BNST infusion of 10.0 μg propranolol impaired retention of the inhibitory avoidance response. The memory enhancing effect of 1.0 μg norepinephrine was attenuated by 5.0 μg propranolol. Intra-BNST infusion of 0.02 μg norepinephrine and 0.2 μg L-glutamate, in which either drug by itself had no discernible effect, enhanced inhibitory avoidance retention if given concurrently right after training. The amnestic effect of APV in the inhibitory avoidance task could be ameliorated by 0.02 μg norephinephrine, which by itself caused no enhancing effect. The memory enhancing effect of L-glutamate was not attenuated by prazosin, but ameliorated by propranolol. These findings suggest that in the inhibitory avoidance task, the glutamate released in the BNST could modulate memory processes through NMDA receptors. Furthermore, release of norepinephrine in the BNST, which may be regulated by presynaptic NMDA receptors, could act on postsynapticβ-adrenergic receptors in modulating memory consolieation processes.

並列關鍵字

β-adrenergic receptors ； avoidance learning ； bed nucleus of the stria terminalis ； NMDA receptors ； glutamate ； norepinephrine

參考文獻

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