Medial Entorhinal VIP-expressing interneurons receive direct input from Anterior Dorsal Thalamus and are critical for spatial memory

Abstract

Head-direction (HD) cells are found across several regions in the brain, including the anterodorsal thalamic nucleus (ADN), the subicular complex, and the medial entorhinal cortex (MEC). A fundamental role of head direction cells is to provide input to MEC grid cells, which are thought to translate information about head direction into a metric code for spatial location. However, classic anatomical studies indicate that most thalamic HD projections pass indirectly to the MEC via the post- and para-subiculum, with only a small subset of ADN fibers terminating in the MEC. To further investigate the smaller and direct projection to the MEC, we use rabies-mediated retrograde tracing in mice to determine if this projection explicitly targets a subset of MEC neurons. Our findings reveal that ADN neurons specifically project onto MEC interneurons, with a preference for MEC VIP-expressing cells. Additionally, MEC VIP cells receive input from the hippocampus, the subicular complex, and the retrosplenial cortex - key centers for spatial memory - suggesting a specialized role for MEC VIP cells in spatial memory. Indeed, we find that MEC VIP cells exhibit increased c-Fos expression in a spatial memory task and show that chemogenetic inhibition of these neurons impairs task performance. Together, these data uncover a specific projection of head direction information onto MEC interneurons and confirm that MEC VIP-expressing cells are critical for spatial memory.