Hippocampal sequences traverse a memory space

Highly reliable sequential dynamics organize neural activity in the hippocampus and progress with changes in physical, sensory, or cognitive variables, typified by place cells during active exploration. But sensory and behavioral variables are often confounded, and so it remains intensely debated whether hippocampal sequences are driven by sensory content directly or rather reflect the alignment of internally generated dynamics to external perception. Here we used mouse virtual reality to characterize hippocampal dynamics in environments of systematically different sensory complexity, and to test the robustness of neural sequences to manipulations of exact sensory content. The structure of neural sequences was perturbed by changes in both moment-to-moment sensation and ongoing behavior, in a pattern that was best explained by the different memory strategies employed by the animal in each context. Neural subsequences could be flexibly interrupted, inserted, and resumed wherever a memory of prior experience was violated, indicating that the propagation of hippocampal dynamics was not rigidly fixed by internal networks and initial conditions. Rather, we argue that hippocampal sequences explore an abstract memory space of selectively remembered experiences, which flexibly encompasses both sensory and internal factors in a context-dependent manner.