Dentate granule cell activity and slow gamma oscillations support the formation of precise memories
1 IEECR, Bonn
Animals constantly form memories and often, also very subtle differences in their environment are worth remembering. How does the brain compute these very similar, overlapping inputs and converts them into more distinct and memorable patterns? In the mammalian brain, a candidate area for this process, termed pattern separation, is the dentate gyrus. It is part of the hippocampal formation and receives strong inputs from the entorhinal cortex, a major hub for multisensory information in the brain. We used a dentate-specific optogenetic inhibition strategy combined with a spatial object pattern separation test, to show that in mice, unperturbed dentate activity during the acquisition phase is required for successful memory formation. Adding in-vivo electrophysiology to that, we found that dentate granule cell inhibition, however, does not alter the LFP profile in CA1, a major output area of the hippocampus. A computational model of the hippocampus suggested that dentate granule cells might perform pattern separation best when they receive input from the entorhinal cortex in the slow gamma range. To test this, we used optogenetic stimulation of PV-positive neurons in the medial septum to entrain the brain to different oscillations. We found that slow gamma, but not slow or fast theta stimulation, led to an improved performance in the object pattern separation test. In addition, mice that received slow gamma stimulation moved more and faster, and explored more, suggesting that entraining the brain to slow gamma frequencies puts the mouse in an exploratory state, where pattern separation is best performed when most necessary.