Rossato Janine I, Gonzalez Maria Carolina, Apolinário Gênedy, Radiske Andressa, Brisa Elis, Carneiro Livia Maria, Cammarota Martín
Memory Research Laboratory - Brain Institute and Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, Brazil.
International Institute of Neuroscience, Macaiba, Brazil.
Eur J Neurosci. 2025 Mar;61(5):e70049. doi: 10.1111/ejn.70049.
Object recognition memory (ORM) is a hippocampus-dependent form of memory essential for distinguishing items and constructing episodic representations of the past. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine-specific protein kinase highly enriched in the hippocampal formation, where it acts as a memory-relevant calcium effector. We found that, in rats, training in an ORM inducing learning task rapidly increased CaMKII autophosphorylation in the CA1 region of the dorsal hippocampus. Moreover, early post-acquisition intra-dorsal CA1 injection of the substrate-competitive CaMKII inhibitor AIP impaired long-term ORM without affecting short-term ORM or previously consolidated ORMs. The amnesia induced by AIP was replicated by the calmodulin-competitive CaMKII inhibitor KN93, but not by the inactive analogues of either KN93 or AIP. Notably, these effects occurred regardless of the subject's sex and age or the time of day when learning took place. Together, our findings indicate that hippocampal CaMKII activity is necessary shortly after training for the normal consolidation of ORM.
物体识别记忆（ORM）是一种依赖海马体的记忆形式，对于区分事物和构建过去的情景表征至关重要。钙/钙调蛋白依赖性蛋白激酶II（CaMKII）是一种丝氨酸/苏氨酸特异性蛋白激酶，在海马结构中高度富集，在其中作为与记忆相关的钙效应器发挥作用。我们发现，在大鼠中，进行ORM诱导学习任务的训练会迅速增加背侧海马CA1区的CaMKII自身磷酸化。此外，在习得后早期向背侧CA1区内注射底物竞争性CaMKII抑制剂AIP会损害长期ORM，但不影响短期ORM或先前巩固的ORM。钙调蛋白竞争性CaMKII抑制剂KN93可复制AIP诱导的失忆，但KN93或AIP的无活性类似物则不会。值得注意的是，无论受试者的性别、年龄或学习发生的时间如何，这些效应都会出现。总之，我们的研究结果表明，训练后不久，海马体CaMKII活性对于ORM的正常巩固是必要的。
