Extended Data Fig. 7: Effect of optogenetic disruption of SWRs on firing rates and field potentials, and reactivation of hippocampal cells during SWRs.
From: Hippocampal CA2 sharp-wave ripples reactivate and promote social memory
a, The closed-loop SWR truncation system: two signals (for real positive events—‘ripple band’—and noise) are extracted from the recording board and filtered in the ripple band (100–300 Hz); a waveform rectifier and a low-pass filter are applied (using a CED 1401 device); upon detection of a positive event (real positive event = 1 and noise = 0), two current sources are triggered and light is delivered bilaterally through the optic fibres connected to the animal. b, Estimation of detection performance. Left graph, a subsample of events detected by our on-line system in three sessions (n = 1,000) was validated by ground truth (offline detected events); the plot shows percentage of true positives (SWR) versus false positives (no-SWR). Right graph, a subsample of true events (detected offline) in three sessions (n = 1,000) were cross-validated with our online detector to quantify the percentage of events detected (SWRs disrupted) and missed. c, CA1, CA2 and CA3 LFP patterns during CA2 SWR disruption. d, CA1, CA2 and CA3 average firing responses to normal and truncated SWRs show strong suppression of firing after stimulation with light (blue bar) (n = 53, 148, 87 CA1, CA2, CA3 cells; P < 10−6, 9.7 × 10−7, 1.14 × 10−8, respectively; rank-sign test). e, The firing of CA2 pyramidal cells was suppressed by brief yellow-light pulses (yellow rectangle) in Amigo2–Cre animals expressing AAV2/5 EF1a.DIO.eArch3.0–eYFP in CA2. Curves show mean and s.e.m. (n = 58, P < 0.03; rank-sign test). f, Example session in which 30-s pulses of yellow light (yellow bars) were delivered once every two minutes to the CA2 region of Amigo2–Cre mice expressing eArch3.0. The black trace shows ripple-band (100–300 Hz) power in the CA1 pyramidal layer, and magenta traces shows detected SWRs. Note the suppression of CA1 SWRs during illumination. g, Example session showing the decreased rate of CA2 SWRs owing to photoactivation of eArch3.0 (P < 0.0246; Wilcoxon’s rank-sum test). The yellow dashed line shows the period of light stimulation, and the black and blue traces show SWR rate before and during the period of photostimulation, respectively. h, Social-memory recall was suppressed following CA2 silencing by yellow-light pulses (30 s, once every 2 min) during the post-sleep period in Amigo2–Cre mice injected with AAV–DIO–eArch3.0 (n = 9; discrimination index not significantly different from 0; P > 0.05, t-test), whereas social memory was present in Cre− littermate controls injected with the same virus and receiving the same light pulses (n = 8; discrimination index differed significantly from 0; P < 0.01).
