Navigating the circuitry of the brain's GPS system: Future challenges for neurophysiologists

The discovery of the brain's navigation system creates a compelling challenge for neurophysiologists: how do we map the circuitry of a system that can only be definitively identified in awake, behaving animals? Do grid and border cells in the entorhinal cortex correspond to the two classes of principal cell found there, stellate and pyramidal cells? In the hippocampus, does the diversity seen in pyramidal cell subtypes have functional correlates in the place cell system? How do interneurons regulate the activity of spatially tuned principal cells in the hippocampal and entorhinal circuits? Here, we discuss recent literature relating the cellular circuitry of these circuits to in vivo studies of the brain's navigation system, and the role that interneurons have in regulating the activity of principal cells in these circuits. We propose that studying in vitro models of neuronal oscillations in the entorhinal cortex and hippocampus can provide useful insights for bridging the gap in understanding that exists in relating in vivo and behavioral studies to circuit function at the cellular level.