Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories.
Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories.
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DOI：
10.1093/cercor/bhy142
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发表时间：
2019-06
期刊：
影响因子：
3.7
通讯作者：
N. Yamawaki;K. Corcoran;A. Guedea;G. Shepherd;J. Radulovic
中科院分区：
文献类型：
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作者：
N. Yamawaki;K. Corcoran;A. Guedea;G. Shepherd;J. Radulovic
学习将压力事件与特定的环境背景联系起来取决于海马体的兴奋性传递，但这些信息如何传递到新皮质以进行持久的记忆存储尚不清楚。我们确定了背侧海马 (DH) 向压后皮质 (RSC) 的投射，该投射主要来自下托并包含囊泡谷氨酸转运蛋白 1 (vGlut1) 或 vGlut2。 vGlut1+ 和 vGlut2+ 轴突都强烈兴奋并非突触抑制浅层的 RSC 锥体神经元，但 vGlut2+ 轴突触发更大的抑制并扩散到深层，表明这些途径通过部分冗余、部分分化的细胞机制参与 RSC 回路。利用小鼠的情境恐惧调节来模拟情境联想记忆，并结合化学遗传学轴突沉默，我们发现 vGlut1+ 投射主要参与处理最近的情境记忆，而 vGlut2+ 投射则有助于其长期存储。因此，在 DH→RSC 通路中，vGlut1+ 和 vGlut2+ 回路的参与对恐惧诱发情境记忆的形成和持续有不同的贡献。
Learning to associate stressful events with specific environmental contexts depends on excitatory transmission in the hippocampus, but how this information is transmitted to the neocortex for lasting memory storage is unclear. We identified dorsal hippocampal (DH) projections to the retrosplenial cortex (RSC), which arise mainly from the subiculum and contain either the vesicular glutamate transporter 1 (vGlut1) or vGlut2. Both vGlut1+ and vGlut2+ axons strongly excite and disynaptically inhibit RSC pyramidal neurons in superficial layers, but vGlut2+ axons trigger greater inhibition that spreads to deep layers, indicating that these pathways engage RSC circuits via partially redundant, partially differentiated cellular mechanisms. Using contextual fear conditioning in mice to model contextual associative memories, together with chemogenetic axonal silencing, we found that vGlut1+ projections are principally involved in processing recent context memories whereas vGlut2+ projections contribute to their long-lasting storage. Thus, within the DH→RSC pathway, engagement of vGlut1+ and vGlut2+ circuits differentially contribute to the formation and persistence of fear-inducing context memories.