Environmental enrichment promotes sparse coding in hippocampus via increased dendritic inhibition

Environmental enrichment has been shown to improve hippocampus-dependent spatial learning and memory. However, how enrichment influences hippocampal network activity remains still largely unclear.
Here we used cFos labeling, in vivo Ca2+ imaging and in vitro electrophysiology to study the effect of environmental enrichment onto hippocampal network activity. First, we showed that exploration of novel context leads to increased cFos activity in CA1 and DG in animals housed under both standard and enrichment conditions. Remarkably, the number of cFos cells during exploration was lower in enriched animals. Additionally, we recorded Ca2+ responses from CA1 pyramidal cells with miniature microscope from mice exploring familiar and novel contexts. The analysis of cell responses revealed lower firing frequency in PCs of enriched animals. This indicates that enrichment does not increase overall hippocampal activity but improves sparse coding in hippocampus.
To understand the underlying mechanisms, we explored the possibilities that inhibitory interneurons are involved. We found that enrichment leads to increased activation of dendrite-targeting somatostatin-expressing (SOM) interneurons during exploration, which was linked to changes in the activity levels of principal neurons in CA1. This is not due to changes in intrinsic properties of SOM interneurons, but due to larger number of glutamatergic synapses onto SOM interneurons. At the functional level, it is accompanied by increased synaptic connectivity between pyramidal cells and SOM interneurons, as we show by performing whole-cell patch-clamp recordings from SOM interneurons while stimulating pyramidal cell axons in brain slices from control and enriched mice. Furthermore, we observed increased lateral feedback inhibition in enrichment in vitro.
Using simultaneous in vivo Ca2+ imaging from pyramidal cells and optogenetic silencing of SOM interneurons in CA1 in mice during spatial exploration, we found that SOM interneurons have a big impact on the firing frequency of PCs and the number of active cells. Most importantly, the effect of silencing on the number of active cells is stronger in enrichment.
Taken together, our data show that environmental enrichment decreases the size of hippocampal cell assemblies via enhanced recruitment of dendrite-targeting SOM interneurons.