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通过联合运动学习对海马神经细胞粘附分子进行依赖于习得的调节。

Acquisition-dependent modulation of hippocampal neural cell adhesion molecules by associative motor learning.

作者信息

Navarro-López Juan D, Contreras Ana, Touyarot Katia, Herrero Ana I, Venero César, Cambon Karine, Gruart Agnés, Delgado-García José M, Sandi Carmen, Jiménez-Díaz Lydia

机构信息

Laboratory of Neurophysiology and Behavior, Facultad de Medicina de Ciudad Real, Universidad de Castilla-La Mancha, Ciudad Real, Spain.

INRAE, Bordeaux INP, NutriNeuro, University of Bordeaux, Bordeaux, France.

出版信息

Front Neuroanat. 2022 Dec 21;16:1082701. doi: 10.3389/fnana.2022.1082701. eCollection 2022.

Abstract

It is widely accepted that some types of learning involve structural and functional changes of hippocampal synapses. Cell adhesion molecules neural cell adhesion molecule (NCAM), its polysialylated form polysialic acid to NCAM (PSA-NCAM), and L1 are prominent modulators of those changes. On the other hand, trace eyeblink conditioning, an associative motor learning task, requires the active participation of hippocampal circuits. However, the involvement of NCAM, PSA-NCAM, and L1 in this type of learning is not fully known. Here, we aimed to investigate the possible time sequence modifications of such neural cell adhesion molecules in the hippocampus during the acquisition of a trace eyeblink conditioning. To do so, the hippocampal expression of NCAM, PSA-NCAM, and L1 was assessed at three different time points during conditioning: after one (initial acquisition), three (partial acquisition), and six (complete acquisition) sessions of the conditioning paradigm. The conditioned stimulus (CS) was a weak electrical pulse separated by a 250-ms time interval from the unconditioned stimuli (US, a strong electrical pulse). An acquisition-dependent regulation of these adhesion molecules was found in the hippocampus. During the initial acquisition of the conditioning eyeblink paradigm (12 h after 1 and 3 days of training), synaptic expression of L1 and PSA-NCAM was transiently increased in the contralateral hippocampus to the paired CS-US presentations, whereas, when the associative learning was completed, such increase disappeared, but a marked and bilateral upregulation of NCAM was found. In conclusion, our findings show a specific temporal pattern of hippocampal CAMs expression during the acquisition process, highlighting the relevance of NCAM, PSA-NCAM, and L1 as learning-modulated molecules critically involved in remodeling processes underlying associative motor-memories formation.

摘要

人们普遍认为,某些类型的学习涉及海马体突触的结构和功能变化。细胞黏附分子神经细胞黏附分子(NCAM)、其多唾液酸化形式多唾液酸-NCAM(PSA-NCAM)和L1是这些变化的重要调节因子。另一方面,痕迹眨眼条件反射是一种关联性运动学习任务,需要海马体回路的积极参与。然而,NCAM、PSA-NCAM和L1在这种类型的学习中的作用尚未完全明确。在这里,我们旨在研究在痕迹眨眼条件反射习得过程中海马体中这些神经细胞黏附分子可能的时序变化。为此,在条件反射的三个不同时间点评估海马体中NCAM、PSA-NCAM和L1的表达:在条件反射范式的一次(初始习得)、三次(部分习得)和六次(完全习得)训练后。条件刺激(CS)是一个弱电脉冲,与非条件刺激(US,一个强电脉冲)相隔250毫秒的时间间隔。在海马体中发现了这些黏附分子的习得依赖性调节。在条件反射眨眼范式的初始习得期间(训练1天和3天后12小时),与配对的CS-US呈现相对侧的海马体中,L1和PSA-NCAM的突触表达短暂增加,而当关联性学习完成时,这种增加消失,但发现NCAM有明显的双侧上调。总之,我们的研究结果显示了习得过程中海马体细胞黏附分子表达的特定时间模式,突出了NCAM、PSA-NCAM和L1作为学习调节分子在关联性运动记忆形成基础的重塑过程中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b970/9811386/4a4bcc66f833/fnana-16-1082701-g001.jpg

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