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N-甲基-D-天冬氨酸(NMDA)或5-羟色胺(5-HT)受体拮抗剂会损害记忆巩固,并引发各种类型的失忆症。

NMDA or 5-HT receptor antagonists impair memory reconsolidation and induce various types of amnesia.

作者信息

Nikitin V P, Solntseva S V, Kozyrev S A, Nikitin P V, Shevelkin A V

机构信息

P.K. Anokhin Institute of Normal Physiology, Moscow, Russian Federation.

P.K. Anokhin Institute of Normal Physiology, Moscow, Russian Federation.

出版信息

Behav Brain Res. 2018 Jun 1;345:72-82. doi: 10.1016/j.bbr.2018.02.036. Epub 2018 Feb 27.

Abstract

Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning. During the early period of amnesia (<10th day), the unpaired presentation of conditioned stimuli (CS) or unconditioned stimuli (US) in the same training context did not have an effect on both types of amnesia. Retraining an on 1st or 3rd day of amnesia induction facilitated memory formation, i.e. the number of CS + US pairings was lower than at initial training. On the 10th or 30th day after the MET/reminder, the number of CS + US pairings did not change between initial training and retraining. Retraining on the 10th or 30th day following the MK-801/reminder in the same or a new context of learning resulted in short, but not long-term, memory, and the number of CS + US pairings was higher than at the initial training. This type of amnesia was specific to the CS we used at initial training, since long-term memory for another kind of CS could be formed in the same snails. The attained results suggest that disruption of memory reconsolidation using antagonists of serotonin or NMDA glutamate receptors induced amnesias with different abilities to form long-term memory during the late period of development.

摘要

阐明失忆机制是神经科学中的核心问题之一,具有巨大的实际应用价值。此前,我们发现条件性食物呈现与神经递质受体拮抗剂或蛋白质合成抑制剂注射相结合会导致失忆诱导。在本研究中,我们调查了两种失忆的时间进程和特征:在接受食物厌恶条件训练的蜗牛身上,使用NMDA谷氨酸受体拮抗剂(MK - 801)和5 - 羟色胺受体拮抗剂(甲硫噻平,MET)损害记忆再巩固所诱导的失忆。在失忆早期(<第10天),在相同训练环境中未配对呈现条件刺激(CS)或非条件刺激(US)对两种类型的失忆均无影响。在失忆诱导的第1天或第3天进行重新训练有助于记忆形成,即CS + US配对的次数低于初始训练时。在MET/提示后的第10天或第30天,初始训练和重新训练之间CS + US配对的次数没有变化。在MK - 801/提示后的第10天或第30天,在相同或新的学习环境中进行重新训练会产生短期而非长期记忆,并且CS + US配对的次数高于初始训练时。这种类型的失忆特定于我们在初始训练中使用的CS,因为在相同的蜗牛中可以形成对另一种CS的长期记忆。所获得的结果表明,使用5 - 羟色胺或NMDA谷氨酸受体拮抗剂破坏记忆再巩固会在发育后期诱导出具有不同长期记忆形成能力的失忆。

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