Burke Sara N, Maurer Andrew P, Yang Zhiyong, Navratilova Zaneta, Barnes Carol A
Evelyn F. McKnight Brain Institute, Life Sciences North Building, Room 384, University of Arizona, Tucson, AZ 85724, USA.
Behav Neurosci. 2008 Jun;122(3):535-48. doi: 10.1037/0735-7044.122.3.535.
Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally induced expression of neuronal plasticity uses an NMDAR-dependent, LTP-like mechanism and could be used by hippocampal networks to store information. Aged spatial memory-impaired rats exhibit defective experience-dependent place field expansion plasticity. One possible explanation for this aged-associated deficit is alterations in glutamatergic function. In fact, both NMDAR- and AMPAR-mediated field excitatory postsynaptic potentials in CA1 decrease with aging. The current study investigated whether modulation of either AMPA or NDMA receptor activity could restore this experience-dependent plasticity by prolonging AMPAR activity with the ampakine CX516 and modulating the NMDAR with the noncompetitive antagonist memantine. The spatial firing characteristics of multiple CA1 pyramidal cells were monitored under both treatment conditions as aged rats repeatedly traversed a circular track. Compared to the saline baseline condition, acute administration of memantine, but not CX516, reinstated experience-dependent place field expansion. Taken together, these data suggest that pharmacological manipulation of the NMDAR can improve the function of hippocampal networks critical to optimal cognition in aging.
当成年大鼠反复沿着同一路径行进时，海马锥体细胞的位置野会不对称扩展。这种由行为诱导的神经元可塑性表达采用一种依赖NMDAR的、类似长时程增强（LTP）的机制，并且可能被海马网络用于存储信息。老年空间记忆受损大鼠表现出有缺陷的经验依赖性位置野扩展可塑性。这种与年龄相关的缺陷的一种可能解释是谷氨酸能功能的改变。事实上，随着年龄增长，CA1区中由NMDAR和AMPAR介导的场兴奋性突触后电位都会降低。本研究调查了通过使用安帕金CX516延长AMPAR活性以及用非竞争性拮抗剂美金刚调节NMDAR，对AMPA或NDMA受体活性的调节是否能够恢复这种经验依赖性可塑性。在老年大鼠反复穿过圆形轨道的两种治疗条件下，监测多个CA1锥体细胞的空间放电特征。与生理盐水基线条件相比，急性给予美金刚而非CX516，可恢复经验依赖性位置野扩展。综上所述，这些数据表明对NMDAR进行药理学操作可改善对衰老中最佳认知至关重要的海马网络功能。
