Cercato Magali C, Vázquez Cecilia A, Kornisiuk Edgar, Aguirre Alejandra I, Colettis Natalia, Snitcofsky Marina, Jerusalinsky Diana A, Baez María V
Laboratorio de Neuroplasticidad y Neurotoxinas, Instituto de Biología Celular y Neurociencia, Universidad de Buenos Aires (UBA)-CONICET Buenos Aires, Argentina.
Laboratorio de Neuroplasticidad y Neurotoxinas, Instituto de Biología Celular y Neurociencia, Universidad de Buenos Aires (UBA)-CONICETBuenos Aires, Argentina; Ciclo Básico Común-Universidad de Buenos AiresBuenos Aires, Argentina.
Front Behav Neurosci. 2017 Jan 13;10:242. doi: 10.3389/fnbeh.2016.00242. eCollection 2016.
It is widely accepted that NMDA receptors (NMDAR) are required for learning and memory formation, and for synaptic plasticity induction. We have previously shown that hippocampal GluN1 and GluN2A NMDAR subunits significantly increased following habituation of rats to an open field (OF), while GluN2B remained unchanged. Similar results were obtained after CA1-long-term potentiation (LTP) induction in rat hippocampal slices. Other studies have also shown NMDAR up regulation at earlier and later time points after LTP induction or learning acquisition. In this work, we have studied NMDAR subunits levels in the hippocampus and prefrontal cortex (PFC) after OF habituation and after object recognition (OR), to find out whether rising of NMDAR subunits is a general and structure-specific feature during memory formation. In 1, 2 and 3 month old rats there was an increase in hippocampal GluN1 and GluN2A, but not in GluN2B levels 70 min after OF habituation. This rise overlaps with early phase of memory consolidation, suggesting a putative relationship between them. The increases fell down to control levels 90 min after training. Similar results were obtained in the hippocampus of adult rats 70 min after OR training, without changes in PFC. Following OF test or OR discrimination phase, NMDAR subunits remained unchanged. Hence, rising of hippocampal GluN1 and GluN2A appears to be a general feature after novel "spatial/discrimination" memory acquisition. To start investigating the dynamics and possible mechanisms of these changes, we have studied hippocampal neuron cultures stimulated by KCl to induce plasticity. GluN1 and GluN2A increased both in dendrites and neuronal bodies, reaching a maximum 75 min later and returning to control levels at 90 min. Translation and/or transcription and mobilization differentially contribute to this rise in subunits in bodies and dendrites. Our results showed that the NMDAR subunits increase follows a similar time course both and . These changes happen in the hippocampus where a spatial representation of the environment is being formed making possible short term and long term memories (STM and LTM); appear to be structure-specific; are preserved along life; and could be related to synaptic tagging and/or to memory consolidation of new spatial/discrimination information.
人们普遍认为，N-甲基-D-天冬氨酸受体（NMDAR）对于学习和记忆形成以及突触可塑性诱导是必需的。我们之前已经表明，大鼠适应旷场（OF）后，海马中的GluN1和GluN2A NMDAR亚基显著增加，而GluN2B保持不变。在大鼠海马切片中诱导CA1长时程增强（LTP）后也获得了类似的结果。其他研究也表明，在LTP诱导或学习获得后的早期和晚期时间点，NMDAR会上调。在这项工作中，我们研究了OF适应和物体识别（OR）后海马和前额叶皮质（PFC）中的NMDAR亚基水平，以确定NMDAR亚基的增加是否是记忆形成过程中的一个普遍且结构特异性的特征。在1、2和3月龄大鼠中，OF适应70分钟后，海马中的GluN1和GluN2A增加，但GluN2B水平未增加。这种增加与记忆巩固的早期阶段重叠，表明它们之间存在一种假定的关系。训练90分钟后，增加量降至对照水平。在成年大鼠的海马中，OR训练70分钟后也获得了类似的结果，PFC中没有变化。在OF测试或OR辨别阶段后，NMDAR亚基保持不变。因此，海马中GluN1和GluN2A的增加似乎是新的“空间/辨别”记忆获得后的一个普遍特征。为了开始研究这些变化的动态和可能机制，我们研究了用氯化钾刺激以诱导可塑性的海马神经元培养物。GluN1和GluN2A在树突和神经元胞体中均增加，75分钟后达到最大值，并在90分钟时恢复到对照水平。翻译和/或转录以及转运对胞体和树突中亚基的这种增加有不同的贡献。我们的结果表明，NMDAR亚基的增加在[此处原文缺失相关内容]和[此处原文缺失相关内容]中遵循相似的时间进程。这些变化发生在正在形成环境空间表征从而使短期和长期记忆（STM和LTM）成为可能的海马中；似乎是结构特异性的；在整个生命过程中都存在；并且可能与突触标记和/或新空间/辨别信息的记忆巩固有关。
