Hippocampal sharp wave-ripples and 1 the associated sequence replay 2 emerge from structured synaptic 3 interactions in a network model of 4 area CA 3 5

Hippocampal place cells are activated sequentially as an animal explores its 15 environment. These activity sequences are internally recreated (“replayed”), either in the same or 16 reversed order, during bursts of activity (sharp wave-ripples; SWRs) that occur in sleep and awake 17 rest. SWR-associated replay is thought to be critical for the creation and maintenance of 18 long-term memory. In order to identify the cellular and network mechanisms of SWRs and replay, 19 we constructed and simulated a data-driven model of area CA3 of the hippocampus. Our results 20 show that the chain-like structure of recurrent excitatory interactions established during learning 21 not only determines the content of replay, but is essential for the generation of the SWRs as well. 22 We find that bidirectional replay requires the interplay of the experimentally confirmed, 23 temporally symmetric plasticity rule, and cellular adaptation. Our model provides a unifying 24 framework for diverse phenomena involving hippocampal plasticity, representations, and 25 dynamics, and suggests that the structured neural codes induced by learning may have greater 26 influence over cortical network states than previously appreciated. 27