Novelty-induced arousal enhances memory for cued classical fear conditioning: Interactions between peripheral adrenergic and brainstem glutamatergic systems
Novelty-induced arousal enhances memory for cued classical fear conditioning: Interactions between peripheral adrenergic and brainstem glutamatergic systems
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DOI：
10.1101/lm.1513109
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发表时间：
2009-10-01
影响因子：
2
通讯作者：
Williams, Cedric L.
中科院分区：
文献类型：
--
作者：
King, Stanley O., II;Williams, Cedric L.
暴露在新的环境中会提高大脑的唤醒状态和生化变化，以巩固记忆。然而，人们对允许简单地暴露在陌生环境中以提高交感神经输出和改善记忆的过程知之甚少。这一缺陷是通过研究新鲜感引起的外周和/或中枢唤醒如何调节巴甫洛夫恐惧条件反射的记忆来解决的。雄性大鼠暴露于调理室5min或不暴露24 h，然后用5对纯音-电击(0.35 mA)进行预适应。48小时后，在不同的背景下评估保留率。未预先暴露的动物在条件刺激(CS)呈现期间表现出比预先暴露的动物显著更大的冰冻(P<；0.05)。用索他洛尔(6 mg/kg，ip)阻断外周β-肾上腺素能受体，可减弱新颖性对记忆的改善作用。研究2表明，新奇刺激引起的外周自主神经输出的增加是通过与孤束核(NTS)中的脑干神经元突触的内脏传入传递到大脑的。用CNQX(1.0 mU g)阻断NTS的AMPA受体活性，可显著减少非预暴露动物对CS的冷冻作用(P<；0.01)。研究3表明，提高习惯性动物的肾上腺素水平会影响学习，其机制与新奇刺激产生的机制相似。预先给予肾上腺素(0.1 mg/kg)的动物冻结率显著高于生理盐水对照组(P<；0.01)，这种作用可被NTS内注射CNQX减弱。研究结果表明，在预先接触肾上腺素的动物中，新奇刺激诱导的唤醒或增加的交感活动通过肾上腺素能机制增强记忆，这种机制始于外围，并通过迷走神经/NTS复合体集中传递。
Exposure to novel contexts produce heightened states of arousal and biochemical changes in the brain to consolidate memory. However, processes permitting simple exposure to unfamiliar contexts to elevate sympathetic output and to improve memory are poorly understood. This shortcoming was addressed by examining how novelty-induced changes in peripheral and/or central arousal modulates memory for Pavlovian fear conditioning. Male rats were either exposed to the conditioning chamber for 5-min or given no exposure 24 h before conditioning with five tone-shock (0.35 mA) pairings. Retention was assessed 48 h later in a different context. Non-pre-exposed animals exhibited significantly greater freezing during conditioned stimulus (CS) presentations than did pre-exposed animals (P < 0.05). The improvement in retention produced by novelty was attenuated by pretraining a blockade of peripheral beta-adrenergic receptors with sotalol (6 mg/kg, i.p.). Study 2 revealed that novelty-induced increases in peripheral autonomic output are conveyed to the brain by visceral afferents that synapse upon brainstem neurons in the nucleus tractus solitarius (NTS). Blocking AMPA receptor activity in the NTS with CNQX (1.0 mu g) significantly reduced freezing to the CS in non-pre-exposed animals (P < 0.01). Study 3 showed that elevating epinephrine levels in habituated animals influences learning through mechanisms similar to those produced by novelty-induced arousal. Pre-exposed animals given epinephrine (0.1 mg/kg) froze significantly more than saline controls (P < 0.01), and this effect was attenuated by intra-NTS infusion of CNQX. The findings demonstrate that novelty-induced arousal or increasing sympathetic activity with epinephrine in pre-exposed animals enhances memory through adrenergic mechanisms initiated in the periphery and transmitted centrally via the vagus/NTS complex.