Abstract

The medial entorhinal cortex (MEC) is a major center for spatial navigation and memory. We demonstrate that cannabinoid type-1 receptor-expressing GABAergic basket cells selectively innervate principal cells in layer II of the rat MEC that project outside the hippocampus, but avoid neighboring cells giving rise to the perforant pathway to the dentate gyrus. These results show that the organization of GABAergic microcircuits reflects the long-distance axonal targets of principal neurons. Keywords interneuron; cannabinoid; spatial navigation; grid cell; dentate gyrus; GABA Layer II of the medial entorhinal cortex (MEClayerII) is a key part of a distributed network for spatial navigation and memory processing1–4, and it gives rise to the associational glutamatergic pathway known as the perforant path that terminates in the molecular layer of the dentate gyrus5,6. In neocortical and hippocampal networks, a major regulator of principal neurons is the cholecystokinin and cannabinoid type-1 receptor (CB1R)-expressing basket cells (CCKBCs)7. It is generally assumed that basket cells provide perisomatic inhibition to