Rich Experience Boosts Functional Connectome and High-Dimensional Coding in Hippocampal Network

ABSTRACT Challenging the brain with experiential richness creates tissue-level changes and synaptic plasticity, but the interjacent network level has not been accessible. We here show that environmental enrichment has unexpectedly far-reaching effects on network connectivity and multi-dimensional coding in the hippocampus. We present direct evidence that experience impacts local and global network connectivity, synchrony, and rhythmic dynamics. For this, we investigated the hippocampi from standard-housed mice (SD) and mice living in an enriched environment (ENR) using large-scale ex vivo recordings with a high-density microelectrode sensing array that – with the unprecedented spatiotemporal resolution–allowed simultaneous electrophysiological assessment across the entire circuit. In the absence of extrinsic electrical network stimulation, we found enhanced functional connectivity and high-dimensional coding in hippocampal-cortical networks of ENR mice. The mapped connectome illustrated a scale-free smallworld topology and an ENR-induced resilience to random failures. ENR enhanced large-scale spatiotemporal firing patterns, which facilitated efficient pattern separation and boosted the information encoded in the firing phases of slow oscillatory rhythms. Given that essentially all electrophysiological studies on network behaviors have been done on animals housed in stimulus-poor conditions, our SD mice showed the expected normal functionality. The literature consequently underestimates the extent of spontaneous network activity and connectivity under truly physiological conditions. Our results pave the way to unveil fundamental mechanisms of experience-dependent enhancement in the hippocampal network underlying high brain functions and provide markers for large-scale network remodeling and metaplasticity.