From Point A to Point B, and What it Means for Epilepsy

A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice Bohne P, Schwarz MK, Herlitze S, Mark MD. Front Neural Circuits. 2019;13:51. doi:10.3389/fncir.2019.00051. eCollection 2019. 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), and 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 RC and subiculum (S). To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC, and S, which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial, interposed (IntP), and lateral 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. Anatomical and Physiological Foundations of Cerebello-Hippocampal Interaction Watson TC, Obiang P, Torres-Herraez A, et al. Elife. 2019;8:pii: e41896. doi:10.7554/eLife.41896. Multiple lines of evidence suggest that functionally intact cerebello–hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the 2 structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6 to 12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.