Department of Physiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Cereb Cortex. 2019 Jun 1;29(6):2728-2736. doi: 10.1093/cercor/bhy142.
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.
学习将应激事件与特定的环境背景联系起来依赖于海马体中的兴奋性传递，但这种信息如何传递到新皮层以进行持久的记忆存储尚不清楚。我们确定了背侧海马体（DH）投射到后穹窿皮质（RSC）的投射，这些投射主要来自下托和包含囊泡谷氨酸转运体 1（vGlut1）或 vGlut2。vGlut1+和 vGlut2+轴突强烈兴奋并在浅层中抑制 RSC 锥体神经元的双突触，但是 vGlut2+轴突引发更大的抑制作用，扩散到深层，表明这些途径通过部分冗余的、部分分化的细胞机制参与 RSC 回路。我们使用小鼠的情境恐惧条件反射来模拟情境联想记忆，结合化学遗传轴突沉默，发现 vGlut1+投射主要参与处理最近的情境记忆，而 vGlut2+投射则有助于它们的长期存储。因此，在 DH→RSC 通路中，vGlut1+和 vGlut2+回路的参与程度不同，有助于形成和维持引起恐惧的情境记忆。
