Environmental Novelty Modulates Rapid Cortical Plasticity During Navigation

Abstract In novel environments, animals quickly learn to navigate, and position-correlated spatial representations rapidly emerge in both the retrosplenial cortex (RSC) and primary visual cortex (V1). However, the role of plasticity in building these spatial representations, and how experience modulates this process, are not well understood. Here, we investigated the plasticity of spatial representations with real-time, cellular-resolution read and write control of neural activity using two-photon calcium imaging combined with holographic optogenetic stimulation in mice navigating virtual reality environments. Targeted stimulation of individual layer 2/3 neurons rapidly biased neural activity towards stimulation-paired locations in novel, but not familiar, environments. In contrast, RSC layer 5 neurons exhibited stimulation-induced plasticity regardless of environmental familiarity. These findings reveal a layer-specific, experience-dependent modulation of plasticity and offer a framework for how neocortical spatial representations strike a balance between stability of familiar environments with flexibility for continuous updates of relevant context information. Highlights All optical read-write approach reveals experience-dependent plasticity in cortex Stimulating layer 2/3 neurons biases activity in novel but not familiar environments Layer 5 neurons exhibit plasticity regardless of environmental familiarity Competing Interest Statement K.D. is a founder and scientific advisor for Maplight Therapeutics and Stellaromics and a scientific advisor to RedTree LLC and Modulight. All materials and protocols are freely available to nonprofit institutions and investigators.The other authors declare no competing interests.