Island Cells Control Temporal Association Memory

Entorhinal Cell Clusters There is considerable interest in understanding the function of neurons in layer 2 of the medial entorhinal cortex and how they generate their unique firing patterns, which are important in the recall of facts and past events (see the Perspective by Blair ). Ray et al. (p. 891 , published online 23 January) investigated principal cells in layer 2 by immunoreactivity, projection patterns, microcircuit analysis, and assessment of temporal discharge properties in awake, freely moving animals. In tangential sections, pyramidal neurons were clustered into patches arranged in a hexagonal grid—very similar to the patterns observed in grid cell spatial firing. These patches received selective cholinergic innervation, which is critical for sustaining grid cell activity. Kitamura et al. (p. 896 , published online 23 January) found that these cells drive a hippocampal circuit by projecting directly to the hippocampal CA1 area and synapsing with a distinct class of inhibitory neurons. This circuit provides feed-forward inhibition in combination with excitatory inputs from layer 3 cells of the medial entorhinal cortex, projecting to CA1 pyramidal cells to determine the strength and time window of temporal associative inputs.