Potential adaptive function for altered long-term potentiation mechanisms in aging hippocampus.
Potential adaptive function for altered long-term potentiation mechanisms in aging hippocampus.
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DOI：
10.1523/jneurosci.2036-08.2008
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发表时间：
2008-08-06
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影响因子：
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通讯作者：
Kirkwood A
中科院分区：
文献类型：
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作者：
Boric K;Muñoz P;Gallagher M;Kirkwood A
长时程增强（LTP）诱导的年龄相关性改变已有充分记录，这为与衰老相关的记忆衰退提供了可能的神经基础。对神经可塑性的研究对于理解衰老过程中个体差异的神经基础也很重要，这些个体差异包括从明显的认知障碍到与年轻人功能相当的情况。为了研究区分这些结果的细胞机制，我们研究了在海马依赖性空间学习中行为特征不同的雄性远交系年轻和老年大鼠的LTP诱导情况。我们在体外评估了在谢弗侧支到CA1突触诱导的N - 甲基 - D - 天冬氨酸受体（NMDAR）依赖性和非依赖性形式的LTP的幅度。我们发现，在整个认知结果范围内，年龄显著降低了NMDAR依赖性LTP，而NMDAR非依赖性LTP的增加仅在表现良好的老年大鼠中明显。此外，在年轻大鼠中，行为表现与NMDAR - LTP的幅度密切相关，而NMDAR非依赖性LTP仅在老年大鼠中与行为表现相关。结合之前在该模型中关于长时程抑制（LTD）机制的类似发现，这些结果支持这样一种观点，即衰老过程中神经可塑性从NMDAR依赖性机制向NMDAR非依赖性机制的转变与更好的认知结果相关。
Age-dependent alterations in the induction of long-term potentiation (LTP) are well documented, providing a likely neural basis for memory decline associated with aging. Studies of neural plasticity are also important to understand the neural basis of individual differences in aging, ranging from significant cognitive impairment to preservation of function on a par with younger adults. To examine the cellular mechanisms that distinguish such outcomes, we studied the induction of LTP in male outbred young and aged rats behaviorally characterized in hippocampal-dependent spatial learning. We evaluated, in vitro, the magnitude of NMDA receptor (NMDAR)-dependent and -independent forms of LTP induced in the Schaffer collateral to CA1 synapses. We found that age substantially reduces NMDAR-dependent LTP across the spectrum of cognitive outcomes, whereas increased NMDAR-independent LTP occurs distinctively in high-performing aged rats. Moreover, in young rats, behavioral performance correlates strongly with the magnitude of NMDAR-LTP, whereas NMDAR-independent LTP correlates with behavioral performance only in aged rats. Together with similar previous findings on the mechanisms for LTD in this model, these results support the notion that a shift from NMDAR-dependent to NMDAR-independent mechanisms for neural plasticity during aging is associated with better cognitive outcomes.