Rapid formation of non-spatial hippocampal representations consistent with behavioral timescale synaptic plasticity is modulated by entorhinal input

Abstract Behavioral timescale synaptic plasticity (BTSP) is a form of synaptic potentiation where a single plateau potential in hippocampal neurons forms a place field during spatial learning. However, it remains unknown whether BTSP also forms non-spatial responses and what roles the medial and lateral entorhinal cortex (MEC and LEC) play in driving non-spatial BTSP. Using two-photon calcium imaging of CA1 pyramidal neurons in mice learning an odor-cued working memory task, we observed spontaneously-occurring large plateau-like calcium events during odor cues, forming stable odor representations. Using holographic optogenetics, we induced similar plateau-like calcium events in single neurons that were followed by novel odor representations. Chemogenetic inhibition of MEC reduced the frequency of plateau-like events, whereas LEC inhibition reduced their efficiency in forming odor representations. Together, our findings demonstrate that rare large somatic calcium events, consistent with BTSP, precede and drive novel odor representations in a manner differentially regulated by medial and lateral entorhinal cortex.