Path integration (PI) is a highly conserved, self-motion-based navigation strategy. Since the discovery of grid cells in the medial entorhinal cortex, neurophysiological data and computational models have suggested that these neurons serve PI. However, more direct empirical evidence supporting this hypothesis has been missing due to a lack of selective manipulations of grid cell activity and suitable behavioral assessments. Here we report that selective disruption of grid cell activity in mice can be achieved by removing NMDA glutamate receptors from the retro-hippocampal region and that disrupted grid cell firing accounts for impaired PI performance. Notably, the genetic manipulation did not affect the activity of other spatially selective cells in the medial entorhinal cortex and the hippocampus. By directly linking grid cell activity to PI, these results contribute to a better understanding of how grid cells support navigation and spatial memory.

SummaryThe motor cortico-basal ganglion loop is critical for motor planning, execution, and learning. Balanced excitation and inhibition in this loop is crucial for proper motor output. Excitatory neurons have been thought to be the only source of motor cortical input to the striatum. Here, we identify long-range projecting GABAergic neurons in the primary (M1) and secondary (M2) motor cortex that target the dorsal striatum. This population of projecting GABAergic neurons comprises both somatostatin-positive (SOM+) and parvalbumin-positive (PV+) neurons that target direct and indirect pathway striatal output neurons as well as cholinergic interneurons differentially. Notably, optogenetic stimulation of M1 PV+ and M2 SOM+ projecting neurons reduced locomotion, whereas stimulation of M1 SOM+ projecting neurons enhanced locomotion. Thus, corticostriatal GABAergic projections modulate striatal output and motor activity.