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Theta sequences of hippocampal activity supports planning and prediction, and in CA1 they are shaped by CA3 and entorhinal (layer III) inputs. We targeted entorhinal inputs with highly specific optogenetic inhibition, leaving the remaining circuit intact. While CA1 spatial coding properties were largely unaffected, the slope and range of theta phase precession were impaired. Surprisingly, theta sequences were strengthened. These results suggest that sequence organization is not a simple consequence of precession and depends on circuit-level dynamics across the trisynaptic circuit, while direct entorhinal inputs may act as a supervisory signal driving learning and representational updates.
Guardamagna et al. (Fri,) studied this question.