Sleep deprivation and hippocampal ripple disruption after one-session learning eliminate memory expression the next day

Abstract

Memory reactivation during non-rapid-eye-movement ripples is thought to communicate new information to a systems-wide network and thus can be a key player mediating the positive effect of sleep on memory consolidation. Causal experiments disrupting ripples have only been performed in multiday training paradigms, which decrease but do not eliminate memory performance, and no comparison with sleep deprivation has been made. To enable such investigations, we developed a one-session learning paradigm in a Plusmaze and show that disruption of either sleep with gentle handling or hippocampal ripples with electrical stimulation impaired long-term memory. Furthermore, we detected hippocampal ripples and parietal high-frequency oscillations after different behaviors, and a bimodal frequency distribution in the cortical events was observed. Faster cortical high-frequency oscillations increased after normal learning, a change not seen in the hippocampal ripple-disruption condition, consistent with these having a role in memory consolidation.

Keywords: consolidation; cortical ripples; memory; ripples; sleep.

Fig. 1.

Sleep deprivation and hippocampal ripple disruption. (A) Animals were trained in the Plusmaze and were either sleep deprived (gentle handling) or allowed to sleep for 4 h and then retested 24 h later (no food present). Only after sleep and not sleep deprivation (Sleep-D), the animals remembered the previous day’s goal location. (B) As A but now implanted animals were trained in the Plusmaze and then received sharp-wave ripple disruption (SWR-D), control disruption (200 ms delay, Con-D), or no-disruption (No-D) for 4 h. Only with intact hippocampal ripples, the animals remembered the previous day’s goal location. Performance as % choice, with 100% no wrong arm entry and −25% for each arm entry. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 2.

Behavior and NonREM (NREM) ripples and high-frequency oscillations. (A) Study design. Three animals underwent three different behavioral conditions in the event arena: Foraging on a linear track with chocolate crumbs (F, 1.5 m × 15 cm, 20 min), Novelty experience (N, 1.5 × 1.5 m open-field with novel objects/textures, 20 min), and Plusmaze (PM, 1.5 × 1.5 m, 10 min free exploration, then 15 trials to goal with chocolate cereal). We recorded a 4 h sleep period after these behaviors and a nonlearning Baseline (B). (B) We detected ripple events in the hippocampus (yellow, HPC) and high-frequency oscillations in the right posterior parietal cortex (black, PPC) during NonREM sleep and classified events into single HPC, co-occurring HPC-PPC, and single PPC. There were more HPC-PPC and more PPC events after Plusmaze training than other behaviors. (C) Histogram of hippocampal ripples (HPC) and parietal high-frequency oscillations (PPC-HFO). For the latter, the distribution was bimodal, and they were thus divided by ∼155 Hz (individual threshold, slow high-frequency oscillations [sHFO], fast high-frequency oscillation [fHFO]). (D) After Plusmaze training, the largest increase was seen in the fast single PPC events. (E) and (F) Example traces of slow and fast PPC-HFO events both filtered for 100–250 Hs and raw local field potential (LFP) trace. Baseline (B), Foraging (F), Novelty (N), and Plusmaze (PM). *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 3.

Spectral power and Granger during events: (A) Spectrogram for all three brain areas (Top, hippocampus; Middle, parietal cortex; and Bottom, prefrontal cortex) for three event types for 100–250 Hz ±100 ms (same color scale all events) and average event trace (above). On the Right, statistical contrast of slow HFO vs. ripples, fast HFO vs. ripples, and fast vs. slow HFOs with cluster-based correction for multiple comparison (red, first event higher power; blue, second event higher power). (B–D) For all three brain areas normalized power (for each animal across event type and brain area) for 100–250 Hz ±50 ms around the events in each condition (same number of events across conditions for each type). (B) Hippocampus (HPC), (C) posterior parietal cortex (PPC), and (D) prefrontal cortex (PFC). Overall, the three event types differed in their spectral profiles across brain areas. Individual hippocampal ripples showed large hippocampal power but less cortical; slow PPC-HFO showed less hippocampal power but more cortical power than hippocampal ripples. Finally, fast PPC-HFO showed larger PFC but smaller HPC spectral power. These general effects were the same if separated for those cortical events that were classified as coupled or not coupled to hippocampal ripples (see SI Appendix, Fig. S4). As for condition effect, there was an increase in power after Plusmaze training in PPC and PFC for the fast cortical events. (E and F) Granger causality analysis (parametric) is shown for both 0–20 Hz and 20–300 Hz oscillation bands for the different event types (single hippocampal ripples HPC [yellow], slow [black and white shading], and fast [black shading] posterior parietal cortex high-frequency oscillations [PPC-HFO]) with the six possible directionalities. (E) In the slower frequencies, fast PPC-HFO induced an increase in prefrontal cortex to hippocampal and to parietal Granger values (linear increase from ripples, slow and fast HFO). (F) In contrast, in the faster frequency band, overall PFC to PPC was increased for all events and PPC-HFO showed an increase in PFC to HPC values (linear increase from ripples, slow and fast HFO). (G) Granger for selected bands focused on PFC to PPC (Left) and PFC to HPC (Right). Prefrontal cortex, PFC; hippocampus, HPC; posterior parietal cortex, PPC. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 4.

Spindle coupling during events: We detected delta waves (A), spindles (B), and delta-spindle coupled event (C) in the two cortical areas (prefrontal cortex [PFC] and parietal cortex [PPC]). (D) Across conditions, there was no change in spindle-ripple coupling, but there was an increase in high-frequency oscillation to spindle coupling after Plusmaze training for both slow (E) and fast (F) events. (G) Example traces for spindle coupling with high-frequency oscillations and hippocampal ripples. (H) We calculated the percentage of each co-occurring event; of note is the change in axis for the different event groupings. From Left to Right are the percentages of ripples that occur before, during, or after a PPC spindle; the percentage of PPC spindles that have a ripple before, during, or after; the percentage of HFOs that occur with a ripple; and the percentage of HFOs that occur during PPC spindles. Next, the figure has the percentage of ripples that occur with a HFO and the percentage of PPC spindles that have a slow or fast HFO. Above the figure are P values of contrasts. (I) HFOs after disruption conditions. Sharp-wave ripple disruption (SWR-D, n = 5 animals from Fig. 1) led to a decrease of both slow and fast HFOs in PPC. Baseline (B), Foraging (F), Novelty (N), Plusmaze (PM), *P < 0.05, **P < 0.01, ***P < 0.001.