以大白鼠躲避反應作業探討情緒記憶的神經機制

NEURAL MECHANISMS UNDERLYING AFFECTIVE MEMORY OF THE INHIBITORY A VOIDANCE RESPONSE IN RATS

本實驗室利用抑制型躲避作業研究大白鼠學習與記憶的神經機制，本文回顧多年的實驗結果，並從其隱含意義探討情緒記憶神經基礎的一些基本問題。研究結果發現：情緒事件之所以留下強烈的記憶，有賴於多種壓力相關激素對記憶的調節，這些內生性記憶調節因子透過腦中的一些結構（如杏仁核、海馬、藍斑核等），產生促進記憶的作用。這些神經核，一方面能被情緒刺激所啟動而產生各式的情緒反應；另一方面，在學習後以不同的方式操弄這些神經核的功能，會對情緒記憶：產生明顯的影響。這種歷程意涵情緒事件的立即反應與經驗保留，有可能動用相互重疊的神經回路。情緒事件的神經訊息可以由麩安酸神經透過AMPA受體傳至杏仁核內。記憶的形成依賴杏仁核內之NMDA受體興奮，故可能涉及該處之長效增益作用。然此依賴NMDA受體之神經可塑性並非形成情緒記憶的唯一機制。提取新近形成的情緒記憶依賴杏仁核、海馬及終紋床核等結構，但是提取久遠以前的情緒記憶則依賴前額皮質內側與腦島皮質。然而後者並非自前者接收轉移之記憶痕跡，而是自學習伊始便參與記憶形成的歷程。這些研究結果綜合顯示，情緒事件的記憶涉及腦中多重結構，其中一些結構不只負責記憶，也參與情緒經驗或反應的產生。情緒經驗可以透過類似長效增益作用以及其他形式的可塑性造成神經變化，這些變化不只產生於一處。多重的記憶痕跡在保留的過程中，隨時間遞嬗產生彼消我長的動態變化：「邊緣系統」的角色漸退而皮質的角色漸增。根據這些實驗的結果與其引伸的意義，當心理學家在構思記憶運作的模式與選擇研究記憶的策略時，神經系統如何處理記憶的問題應是一項重要的考慮因素。

This review intends to integrate our findings on neural processes underlying acquisition, consolidation and retrieval of inhibitory avoidance memory in rats, and to discuss their implications on some fundamental issues concerning the neural substrate of affective memory. Our results suggest that enduring memory for emotional events relies on memory-enhancing effects of stress-released hormones or neurotransmitters, such as epinephrine, corticotropin releasing factor, and central norepinephrine, which exert their influences on memory directly or indirectly via the amygdala, hippocampus, locus coeruleus, etc. These structures are involved not only in formation of emotional memory but also in routine processing of threatening stimuli and initiating emotional responses. Blocking AMPA or NMDA receptors in the amygdala impaired inhibitory avoidance memory, suggesting that glutamate fibers provide the amygdala with sensory information and may induce some form of neural plasticity such as long-term potentiation. However, formation of emotional memory is not exclusively mediated by NMDA-dependent neural plasticity, because norepinephrine could attenuate the amnesia caused by blockade of NMDA receptors. Retrieval of recent (1-day) and remote (21-day) emotional memory depended upon the amygdala and the medial prefrontal cortex, respectively. Because the medial ·prefrontal cortex was also engaged during training and played a role in establishing a long-term trace, it is suggested that for an emotional experience, multiple memory traces with dynamic courses are formed in the brain to retain the experience for various lengths of retention intervals. These findings suggest that an affective experience engages multiple brain structures, activates various forms of neural plasticity, and establishes compound traces with different temporal dynamics. Such information on how the brain processes and stores emotional events in rats may contribute to our construction of functional models for human memory.