The CA3 and CA1 principal cell fields of the hippocampus are vulnerable to aging, and age-related dysfunction in CA3 may be an early seed event closely linked to individual differences in memory decline. However, whether the differential vulnerability of CA3 and CA1 is associated with broader disruption in network-level functional interactions in relation to age-related memory impairment, and more specifically, whether CA3 dysconnectivity contributes to the effects of aging via CA1 network connectivity, has been difficult to test. Here, using resting-state fMRI in a group of aged rats uncontaminated by neurodegenerative disease, aged rats displayed widespread reductions in functional connectivity of CA3 and CA1 fields. Age-related memory deficits were predicted by connectivity between left CA3 and hippocampal circuitry along with connectivity between left CA1 and infralimbic prefrontal cortex. Notably, the effects of CA3 connectivity on memory performance were mediated by CA1 connectivity with prefrontal cortex. We additionally found that spatial learning and memory were associated with functional connectivity changes lateralized to the left CA3 and CA1 divisions. These results provide novel evidence that network-level dysfunction involving interactions of CA3 with CA1 is an early marker of poor cognitive outcome in aging.

中文翻译：

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海马 CA3 的功能连接通过 CA1 前额电路预测神经认知老化。

海马的 CA3 和 CA1 主细胞区容易老化，CA3 的年龄相关功能障碍可能是与记忆力下降的个体差异密切相关的早期种子事件。然而，CA3 和 CA1 的差异脆弱性是否与与年龄相关的记忆障碍相关的网络级功能相互作用的更广泛中断有关，更具体地说，CA3 连接障碍是否通过 CA1 网络连接导致衰老的影响，一直是难以测试。在这里，在一组未受神经退行性疾病污染的老年大鼠中使用静息态 fMRI，老年大鼠表现出 CA3 和 CA1 场功能连接的广泛减少。与年龄相关的记忆缺陷是通过左侧 CA3 和海马回路之间的连接以及左侧 CA1 和边缘下前额叶皮层之间的连接来预测的。值得注意的是，CA3 连接对记忆性能的影响是由 CA1 与前额叶皮层的连接介导的。我们还发现空间学习和记忆与左侧 CA3 和 CA1 分区的功能连接变化有关。这些结果提供了新的证据，即涉及 CA3 与 CA1 相互作用的网络级功能障碍是衰老过程中认知结果不佳的早期标志。我们还发现空间学习和记忆与左侧 CA3 和 CA1 分区的功能连接变化有关。这些结果提供了新的证据，即涉及 CA3 与 CA1 相互作用的网络级功能障碍是衰老过程中认知结果不佳的早期标志。我们还发现空间学习和记忆与左侧 CA3 和 CA1 分区的功能连接变化有关。这些结果提供了新的证据，即涉及 CA3 与 CA1 相互作用的网络级功能障碍是衰老过程中认知结果不佳的早期标志。