Dumas T C, Powers E C, Tarapore P E, Sapolsky R M
Department of Biological Sciences, Stanford University, Stanford, California, USA.
Hippocampus. 2004;14(6):701-9. doi: 10.1002/hipo.10210.
Calcium is a key signaling ion for induction of synaptic plasticity processes that are believed to influence cognition. Mechanisms regulating activity-induced increases in neuronal calcium and related synaptic modifications are not fully understood. Moreover, involvement of specific synapses in discrete aspects of spatial learning remains to be elucidated. We used herpes simplex amplicons to overexpress calbindin D(28k) (CaBP) selectively in dentate gyrus (DG) granule cells. We then examined the effects on hippocampal network activity by recording evoked synaptic responses in vivo and in vitro and analyzing hippocampal-dependent behavior. Relative to Lac-Z- and sham-infected controls, CaBP overexpression increased mossy fiber (MF-CA3) excitatory postsynaptic potentials and reduced paired-pulse facilitation (PPF), suggesting an increase in presynaptic strength. Additionally, CaBP overexpression reduced long-term potentiation (LTP), caused a frequency-dependent inhibition of post-tetanic potentiation (PTP), and impaired spatial navigation. Thus, increasing CaBP levels selectively in the DG disrupts MF-CA3 presynaptic function and impairs spatial cognition. The results demonstrate the power of gene delivery in the study of the neural substrates of learning and memory and suggest that mossy fiber synaptic plasticity is critical for long-term spatial memory.
钙是诱导被认为影响认知的突触可塑性过程的关键信号离子。调节活动诱导的神经元钙增加及相关突触修饰的机制尚未完全明确。此外，特定突触在空间学习离散方面的参与情况仍有待阐明。我们使用单纯疱疹病毒扩增子在齿状回（DG）颗粒细胞中选择性过表达钙结合蛋白D（28k）（CaBP）。然后，我们通过在体内和体外记录诱发的突触反应并分析海马依赖性行为，来研究对海马网络活动的影响。相对于感染Lac-Z和假手术的对照组，CaBP过表达增加了苔藓纤维（MF-CA3）兴奋性突触后电位并降低了双脉冲易化（PPF），表明突触前强度增加。此外，CaBP过表达降低了长时程增强（LTP），引起了强直后增强（PTP）的频率依赖性抑制，并损害了空间导航能力。因此，在DG中选择性增加CaBP水平会破坏MF-CA3突触前功能并损害空间认知。这些结果证明了基因传递在学习和记忆神经基础研究中的作用，并表明苔藓纤维突触可塑性对长期空间记忆至关重要。
