Replay of Behavioral Sequences in the Medial Prefrontal Cortex during Rule Switching

Abstract

Temporally organized reactivation of experiences during awake immobility periods is thought to underlie cognitive processes like planning and evaluation. While replay of trajectories is well established for the hippocampus, it is unclear whether the medial prefrontal cortex (mPFC) can reactivate sequential behavioral experiences in the awake state to support task execution. We simultaneously recorded from hippocampal and mPFC principal neurons in rats performing a mPFC-dependent rule-switching task on a plus maze. We found that mPFC neuronal activity encoded relative positions between the start and goal. During awake immobility periods, the mPFC replayed temporally organized sequences of these generalized positions, resembling entire spatial trajectories. The occurrence of mPFC trajectory replay positively correlated with rule-switching performance. However, hippocampal and mPFC trajectory replay occurred independently, indicating different functions. These results demonstrate that the mPFC can replay ordered activity patterns representing generalized locations and suggest that mPFC replay might have a role in flexible behavior.

Canonical goal-selective representations are absent from prefrontal cortex in a spatial working memory task requiring behavioral flexibility

“…Finally, our results suggest a role for mPFC in working memory tasks by representing task structure in terms of groups of behaviorally related elements (Jung et al, 1998;Yu et al, 2018;Kaefer et al, 2020), consistent with findings that the PFC forms long-term memories of learned stimulus categories (Freedman et al, 2001). Each trial consisted of the following steps: (1) the current goal is randomly assigned and cued with lights; a single, randomly assigned route (bridge) is available; rat gets small reward upon arrival at cued goal; (2) animal returns to center via any route; all routes are blocked upon arrival at center;…”

Hippocampal replay of experience at real-world speeds

“…While the existence of these sequential events is well established, the current consensus is that only a minority (~10-45%) of hippocampal SWRs contain statistically identifiable, sequential replay (10, 24, 35, 40). One might therefore conclude that the retrieval of stored representation during SWRs is limited to sequences of locations, and that all such retrieval events are sequential in nature.…”

Faster than thought: Detecting sub-second activation sequences with sequential fMRI pattern analysis

“…The major advantage of fMRI is that it does not suffer from the low sensitivity to hippocampal activity and limited ability to anatomically localize effects that characterizes EEG and MEG. This is particularly important in the case of replay, which is hippocampus-centered but co-occurs with fast sequences in other parts of the brain including primary visual cortex [12], auditory cortex [15], prefrontal cortex (PFC) [13, 14, 16, 17, 76], entorhinal cortex [77–79], and ventral striatum [80]. Importantly, replay events occurring in different brain areas might not be mere copies of each other, but can differ regarding their timing, content and relevance for cognition [e.g., 16, 17].…”

“…Most famously, memory and planning have been linked to fast replay of representation sequences in the hippocampus, happening approximately within 200 to 300 milliseconds (ms) while the animal is resting or sleeping [e.g., 1–9]. Similar events have been observed during behavior [10, 11], as well as outside of the hippocampus [12–17]. Likewise, internal deliberations during choice are reflected in alternations between orbitofrontal value representations that last less than 100 ms [18] and perceptual learning has been shown to result in sub-second anticipatory reactivation sequences in visual cortex [19–21].…”