Enhanced hippocampal theta rhythmicity and emergence of eta oscillation in virtual reality

Hippocampal theta oscillations in rodents profoundly impact neural activity, spatial coding, and synaptic plasticity and learning. What are the sensory mechanisms governing slow oscillations? We hypothesized that the nature of multisensory inputs is a crucial factor in hippocampal rhythmogenesis. We compared the rat hippocampal slow oscillations in the multisensory-rich real world (RW) and in a body-fixed, visual virtual reality (VR). The amplitude and rhythmicity of the hippocampal ~8 Hz theta were enhanced in VR compared to RW. This was accompanied by the emergence of a ~4 Hz oscillation, termed the eta rhythm, evident in the local field potential (LFP) in VR, but not in RW. Similar to theta, eta band amplitude increased with running speed in VR, but not in RW. However, contrary to theta, eta amplitude was highest in the CA1 cell layer, implicating intra-CA1 mechanisms. Consistently, putative CA1 interneurons, but not pyramidal neurons, showed substantially more eta modulation in VR than in RW. These results elucidate the multisensory mechanisms of hippocampal rhythms and the surprising effects of VR on enhancing these rhythms, which has not been achieved pharmacologically and has significant broader implications for VR use in humans. One Sentence Summary Navigation in virtual reality greatly enhances hippocampal 8Hz theta rhythmicity, and generates a novel, ~4Hz eta rhythm that is localized in the CA1 cell layer and influences interneurons more than pyramidal neurons.