Sharp-wave ripple (SWR) events in the hippocampus replay millisecond-timescale patterns of place cell activity related to the past experience of an animal. Interrupting SWR events leads to learning and memory impairments, but how the specific patterns of place cell spiking seen during SWRs contributes to learning and memory remains unclear. A deeper understanding of this issue will require the ability to manipulate SWR events based on their content. Accurate real-time decoding of SWR replay events requires new algorithms that are able to estimate replay content and the associated uncertainty, along with software and hardware that can execute these algorithms for biological interventions on a millisecond timescale. Here, we develop an efficient estimation algorithm to categorize the content of replay from multiunit spiking activity. Specifically, we apply real-time decoding methods to each SWR event and then compute the posterior probability of the replay feature. We illustrate this approach by classifying SWR events from data recorded in the hippocampus of a rat performing a spatial memory task into four categories: whether they represent outbound or inbound trajectories and whether the activity is replayed forward or backward in time. We show that our algorithm can classify the majority of SWR events in a recording epoch within 20 ms of the replay onset with high certainty, which makes the algorithm suitable for a real-time implementation with short latencies to incorporate into content-based feedback experiments.
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