Congratulations Malcolm!!! Can't wait to read :)

This is amazing 😅

Thank you!!

Thanks so much Kevin!

Thank you, Dan!

Ha, it most definitely is. When you do get a chance, let me know what you think!

Thank you Anna! :)

19/19 And of course, a huge thank you to my postdoc mentor, David Foster, for his guidance and invaluable input along the journey!

I welcome your thoughts and would love to chat with anyone about our findings!

18/19 John had conceived of similar adaptation models of replay and theta sequences before. When we teamed up to look at whether a neuronal fatigue model could explain replay's perplexing ‘past-avoidance’, everything began to click into place.

17/19 This project unfolded like a fun but super challenging puzzle. For a long time we wondered, why would replay avoid the recent past? I want to give a HUGE shout out to co-author John Widloski for his tremendous contribution in helping put the final pieces together.

16/19 When we added a source of facilitation onto cells that had been activated along the animal’s prior path, we were able to subtly increase the rate of retrospective replays overall and recapitulate the eventual emergence of a past bias.

15/19 The model produced replays that both avoided each other and the animal’s recent past (for a period of time related to time constant adaptation). Notably, without an additional input (presumably from MEC), the model did not produce the eventual bias for past-going replays.

14/19 Finally, we considered whether a recurrent network endowed with neuronal fatigue could recapitulate this counterintuitive organization of replay. We found that, in our model, adaptation not only *generates* replay, but it also organizes it.

13/19 We optogenetically (or chemogenetically) shut down MEC as rats consumed reward. We indeed found that retrospective replays became less frequent with MEC suppressed, although they were not altogether abolished.

12/19 How does the prior path eventually become preferentially replayed later in the stopping period? We wondered whether the medial entorhinal cortex, a cortical region highly interconnected with hippocampus, might play a role in biasing replay for the animal’s recent past.

11/19 This made us wonder, would *replay* of a path also fatigue the participating cells and prevent a subsequent replay of the same path? Consistent with the idea, we found that when two replays occur back-to-back (within about 1 sec), the second replay avoids the first.

10/19 We hypothesized that neuronal fatigue effectively takes recently activated place cells ‘out of commission’ for a few seconds. If replay is going to occur after the animal stops, it has to recruit different cells/represent a different path from that just taken.