The Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA.
J Neurosci. 2013 Jul 31;33(31):12670-8. doi: 10.1523/JNEUROSCI.1086-13.2013.
The impact of aging on cognitive capabilities varies among individuals ranging from significant impairment to preservation of function on par with younger adults. Research on the neural basis for age-related memory decline has focused primarily on the CA1 region of the hippocampus. However, recent studies in elderly human and rodents indicate that individual differences in cognitive aging are more strongly tied to functional alterations in CA3 circuits. To examine synaptic plasticity in the CA3 region, we used aged rats behaviorally characterized in a hippocampal-dependent task to evaluate the status of long-term potentiation and long-term depression (LTP and LTD) in the associative/commissural pathway (A/C → CA3), which provides the majority of excitatory input to CA3 pyramidal neurons. We found that, unlike in CA1 synapses, in A/C → CA3 LTP is minimally affected by age. However, two forms of LTD, involving NMDA and metabotropic glutamate receptors (mGluR), are both greatly reduced in age-impaired rats. Age-unimpaired rats, in contrast, had intact mGluR LTD. These findings indicate that the integrity of mGluR-LTD at A/C → CA3 inputs may play a crucial role in maintaining the performance of CA3 circuitry in aging.
衰老是如何影响认知能力的在个体之间存在差异，从认知功能显著受损到与年轻成年人相当的功能保持程度不等。关于与年龄相关的记忆衰退的神经基础的研究主要集中在海马体的 CA1 区域。然而，最近在老年人类和啮齿动物中的研究表明，认知老化的个体差异与 CA3 回路的功能改变更为密切相关。为了研究 CA3 区域的突触可塑性，我们使用在海马体依赖性任务中表现出行为特征的老年大鼠来评估联合/连合通路（A/C→CA3）中的长时程增强和长时程抑制（LTP 和 LTD）的状态，该通路为 CA3 锥体神经元提供了大部分兴奋性输入。我们发现，与 CA1 突触不同，在 A/C→CA3 中，LTP 受年龄的影响极小。然而，涉及 NMDA 和代谢型谷氨酸受体（mGluR）的两种形式的 LTD 在年龄受损的大鼠中均大大减少。相比之下，年龄未受损的大鼠具有完整的 mGluR LTD。这些发现表明，A/C→CA3 输入处的 mGluR-LTD 的完整性可能在维持 CA3 回路在衰老过程中的性能方面发挥关键作用。
