A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice
A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice
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DOI：
10.3389/fncir.2019.00051
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发表时间：
2019-08-09
影响因子：
3.5
通讯作者：
Mark, Melanie D.
中科院分区：
文献类型：
--
作者：
Bohne, Pauline;Schwarz, Martin K.;Mark, Melanie D.
小脑参与了注意力、语言、工作记忆、情绪、目标定向行为和空间导航等认知功能的参与。然而，小鼠海马体和小脑之间的准确连接图仍不清楚。在这里，我们进行了一项示踪研究，以确定小鼠大脑中跨突触、小脑-海马区连接的序列，使用重组腺相关病毒(RAAV)和假型缺失突变狂犬病(RABV)病毒的组合。将顺行rAAV-WGA(小麦胚芽凝集素)-Cre示踪病毒主要注射到依赖Cre的tdTomato报告小鼠的小脑深核(DCN)中，导致在海马CA1神经元、脾后皮质(RSC)、鼻皮质(RC)以及丘脑和小脑区有较强的tdTomato标记。而注射逆行示踪病毒rAAV-TTC(破伤风毒素C片段)-EGFP的海马区，在鼻皮质和下丘脑区可见EGFP阳性细胞。为了确定小脑和海马单-跨突触联系的顺序，我们使用了逆行示踪剂RABV Delta G-EGFP(ENVA)。追踪显示，海马齿状回(DG)与RSC、RC和下丘脑(S)有直接联系，RSC、RC和下丘脑(S)与丘脑背外侧区和腹外侧区有单突触联系。这些丘脑核团与小脑顶核(FN)、中间核(INTP)和外侧核(Lat)直接相连，发现了小鼠脑内从顶核到丘脑背外侧核的新的投射路径。总体而言，我们的发现表明，通过外侧背侧和丘脑腹外侧部与RSC、RC和S建立了新的小脑-海马联系。这些结果加强了小脑通过多突触回路参与空间导航等认知功能的概念。
The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar-hippocampal connections in the mouse brain using combinations of Recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC) as well as thalamic and cerebellar areas. Whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP, displayed eGFP positive cells in the rhinal cortex and subiculum. To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABV Delta G-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC and subiculum (S), which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial (FN), interposed (IntP) and lateral (Lat) nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar-hippocampal connection via the laterodorsal and ventrolateral thalamus to RSC, RC and S. These results strengthen the notion of the cerebellum's involvement in cognitive functions such as spatial navigation via a polysynaptic circuitry.