Sagol Department of Neurobiology, Faculty of Natural Sciences, and the Integrated Brain and Behavior Center, University of Haifa, Haifa, Israel.
Hippocampus. 2024 Nov;34(11):564-574. doi: 10.1002/hipo.23631. Epub 2024 Aug 15.
Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long-term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation. Given the crucial role of the hippocampus in spatial memory processing, it has been observed that spatial memory abilities continue to develop as the hippocampus matures, particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is crucial for the induction of activity-dependent synaptic plasticity and spatial memory formation in both rodents and humans. Although extensive evidence shows the role of NMDA receptors (NMDAr) in spatial memory and synaptic plasticity, the studies addressing the role of NMDAr in spatial memory of juveniles are sparse and mostly limited to adult males. In the present study, we, therefore, aimed to investigate the effects of systemic NMDAr blockade by the MK-801 on spatial memory (novel object location memory, OLM) and hippocampal plasticity in the form of long-term potentiation (LTP) of both male and female juvenile rats. Our results show the sex-dimorphic role of NMDAr in spatial memory and plasticity during juvenility, as systemic NMDAr blockade impairs the OLM and LTP in juvenile males without an effect on juvenile females. Taken together, our results demonstrate that spatial memory and hippocampal plasticity are NMDAr-dependent in juvenile males and NMDAr-independent in juvenile females. These sex-specific differences in the mechanisms of spatial memory and plasticity may imply gender-specific treatment for spatial memory disorders even in children.
早期生活或青少年期是神经发育中最关键的阶段，因为它对长期认知有深远的影响。在这个时期，大脑内部和不同区域之间的连接发生了重大变化，特别是与更复杂行为的发展相伴随。海马体是大脑中经历显著产后重塑的区域之一，包括树突分支、突触形成、复杂棘突的形成和神经元增殖。鉴于海马体在空间记忆处理中的关键作用，人们观察到空间记忆能力在海马体成熟过程中继续发展，特别是在青春期之前。N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体通道对于诱导活动依赖性突触可塑性和空间记忆形成在啮齿动物和人类中都至关重要。尽管有大量证据表明 NMDA 受体（NMDAr）在空间记忆和突触可塑性中的作用，但研究 NMDAr 在青少年空间记忆中的作用的研究很少，而且大多仅限于成年雄性。在本研究中，因此，我们旨在研究系统 NMDA 受体阻断剂 MK-801 对雄性和雌性幼年大鼠的空间记忆（新物体位置记忆，OLM）和海马体可塑性（长时程增强，LTP）的影响。我们的结果表明，NMDA 受体在青少年时期的空间记忆和可塑性中具有性别二态作用，因为系统 NMDA 受体阻断会损害幼年雄性的 OLM 和 LTP，而对幼年雌性没有影响。总之，我们的结果表明，空间记忆和海马体可塑性在幼年雄性中依赖 NMDA 受体，而在幼年雌性中则不依赖 NMDA 受体。这些空间记忆和可塑性机制中的性别特异性差异可能意味着即使在儿童中，也需要针对特定性别进行空间记忆障碍的治疗。
