Functional Connectivity of Hippocampal CA3 Predicts Neurocognitive Aging via CA1-Frontal Circuit
Functional Connectivity of Hippocampal CA3 Predicts Neurocognitive Aging via CA1-Frontal Circuit
复制标题
海马 CA3 的功能连接通过 CA1 额叶回路预测神经认知衰老
DOI：
10.1093/cercor/bhaa008
复制
发表时间：
2020-08-01
期刊：
影响因子：
3.7
通讯作者：
Yang, Yihong
中科院分区：
文献类型：
--
作者：
Liang, Xia;Hsu, Li-Ming;Yang, Yihong
海马的CA3和CA1主细胞区易受衰老的影响，CA3中与年龄相关的功能障碍可能是与记忆衰退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破坏有关，更具体地说，CA3连接障碍是否有助于通过CA1网络连接老化的影响，一直难以测试。在这里，使用静息态功能磁共振成像在一组未受神经退行性疾病污染的老年大鼠中，老年大鼠显示CA3和CA1区域的功能连接广泛减少。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沿着预测与海马相关的记忆缺陷。值得注意的是，CA3连接对记忆表现的影响是通过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表明，涉及CA3与CA1相互作用的网络水平功能障碍是衰老中认知结果不良的早期标志。
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.