Hippocampus-retrosplenial cortex interaction

Hippocampal (HPC) theta oscillation during post-training rapid eye movement (REM) sleep supports spatial learning. Theta also modulates neuronal and oscillatory activity in the retrosplenial cortex (RSC) during REM sleep. To investigate the relevance of theta-driven interaction between these two regions to memory consolidation, we computed the Granger causality within theta range on electrophysiological data recorded in freely behaving rats during REM sleep, both before and after contextual fear conditioning. We found a training-induced modulation of causality between HPC and RSC that was correlated with memory retrieval 24 h later. Retrieval was proportional to the change in the relative influence RSC exerted upon HPC theta oscillation.

figure1

Fig: Experimental protocol and sleep architecture. (a) Experimental design and results. Animals (N = 13) were implanted with matrices of single wires into the hippocampus (HPC) and the retrosplenial cortex (RSC), and recorded 3 h before (pre) and after (post) a contextual fear conditioning protocol (CFC). During training, seven animals underwent standard CFC (shock group), whereas six (sham group) underwent the same experimental steps, except for the foot-shocks during training. Both groups were tested for CFC 24 h after training. Inset: The shock group shows significant fear behavior compared to before training and to the sham group. Average freezing across animals for each group during testing (sham n = 6: training vs test, p = 0.63 and shock n = 7: training vs test, p = 0.02; Wilcoxon signed rank test. Testing: sham n = 6 vs shock n = 7: p = 0.001; Wilcoxon rank-sum test). (b) Sleep architecture throughout pre and post recordings averaged across animals and spanning 4 behavioral states: wake (WK), slow wave sleep (SWS), intermediate sleep (IS), and rapid eye movement (REM) sleep. Data expressed as the percentage (%) of each state per 30 s epochs, 15 s overlap. As expected, animals from the shock group remained awake for the majority of time during the first hours after fear training (time awake during post; 1st: 83.8 ± 2.8%, 2nd: 49.2 ± 9.2%, and 3rd hour: 37.3 ± 7.7%), although the exposure to novelty without foot-shock elicited a similar trend in the sham group (1st: 72.6 ± 7.1%, 2nd: 55.2 ± 8.4%, and 3rd hour: 42.3 ± 10.9%). (c) REM sleep is not significantly reduced after training. Percentage of REM sleep within each period (pre or post) for groups sham (top) and shock (bottom) (pre × post: sham n = 6, p = 0.15; shock n = 7: p = 0.58; Wilcoxon signed rank test). *p < 0.05. Graphs show mean ± SEM (lines/bars ± shades/lines).

Importantly, causality peaked during theta acceleration, in synchrony with phasic REM sleep. Altogether, these results support a role for phasic REM sleep in hippocampo-cortical memory consolidation and suggest that causality modulation between RSC and HPC during REM sleep plays a functional role in that phenomenon.

de Almeida-Filho, D.G., Koike, B.D., Billwiller, F. et al. Hippocampus-retrosplenial cortex interaction is increased during phasic REM and contributes to memory consolidation. Sci Rep 11, 13078 (2021). https://doi.org/10.1038/s41598-021-91659-5

Leave a Reply

Your email address will not be published. Required fields are marked *