GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat.
GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat.
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DOI：
10.3389/fnbeh.2016.00242
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发表时间：
2016
影响因子：
3
通讯作者：
Baez MV
中科院分区：
文献类型：
--
作者：
Cercato MC;Vázquez CA;Kornisiuk E;Aguirre AI;Colettis N;Snitcofsky M;Jerusalinsky DA;Baez MV
NMDA受体（NMDAR）是学习记忆形成和突触可塑性诱导所必需的。我们以前已经表明，海马GluN 1和GluN 2A NMDAR亚基显着增加大鼠习惯于一个开放的领域（OF），而GluN 2B保持不变。在大鼠海马脑片中诱导CA 1-长时程增强（LTP）后也得到了类似的结果。其他研究也表明，在LTP诱导或学习获得后的较早和较晚时间点，NMDAR上调。本研究通过研究在OF习惯化和物体再认（OR）后海马和前额叶皮层（PFC）中NMDAR亚单位的水平，来探讨NMDAR亚单位的升高是否是记忆形成过程中的一个普遍的和结构特异性的特征。在1，2和3个月大的大鼠有海马GluN 1和GluN 2A的增加，但没有在GluN 2B水平后70分钟的习惯。这种上升与记忆巩固的早期阶段重叠，表明它们之间存在假定的关系。训练后90 min，增加下降至对照水平。在成年大鼠海马中，在OR训练后70 min获得类似的结果，PFC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GluN 1和GluN 2A的上升似乎是新的“空间/歧视”记忆获得后的一般特征。为了开始研究这些变化的动力学和可能的机制，我们研究了KCl刺激的海马神经元培养物诱导可塑性。GluN 1和GluN 2A增加树突和神经元体，达到最大75分钟后，并返回到控制水平在90分钟。翻译和/或转录和动员差异有助于这种上升的亚基在机构和树突。我们的结果表明，NMDAR亚基的增加遵循相似的时间过程，在体外和体内。这些变化发生在海马体中，在海马体中形成了对环境的空间表征，从而使短期和长期记忆（STM和LTM）成为可能;这些变化似乎是结构特异性的;沿着生命被保存下来;并且可能与突触标记和/或新的空间/辨别信息的记忆巩固有关。
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 in vitro and in vivo. 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.