Extended Data Fig. 10: Generation of CA2 ripple oscillations enhances social-memory recall.
From: Hippocampal CA2 sharp-wave ripples reactivate and promote social memory
a, LFPs showing ripple activity in CA1 (red), CA2 (green) and CA3 (blue) in response to optogenetic triggering of ripple in CA2. b, Rate of ripples in sessions with optogenetic triggering of SWRs (‘artificial CA2’) was significantly higher than in control sessions (‘spontaneous’) (P < 0.05, rank-sum test). c, Firing rates of all pyramidal cells during spontaneous versus optogenetically triggered CA2 ripples were highly correlated (CA1, n = 67, r = 0.63, P < 10−13; Pearson’s correlation; CA2, n = 147, r = 0.75, P < 3 × 10−22; CA3, n = 40, r = 0.48, P = 0.01). d, Firing-rate gain (increase in firing rate during ripples, divided by average firing rate) of pyramidal cells during spontaneous versus triggered ripples for CA1 (n = 67, r = 0.57, P < 10−6), CA2 (n = 147, r = 0.74, P < 3 × 10−35) and CA3 (n = 40, r = 0.25, P > 0.05). e, Social-discrimination indices for Amigo2–Cre− littermate controls injected with Cre-dependent ChR2 AAV with (n = 6, P > 0.05) and without (n = 10, P > 0.05) light stimulation did not differ. f, Effect of social gain on a neuron’s ripple participation gain (post-sleep participation minus pre-sleep participation, divided by their sum). CA1 and CA2 cells showed greater ripple participation gain for cells with positive versus negative social gain for both spontaneous SWRs (CA1 and CA2, n = 67 and n = 147; P < 0.05 and P < 3.4 × 10−3, respectively) and triggered SWRs (CA1 and CA2, P < 0.05 and P < 2.8 × 10−3, respectively). CA3 ripple participation gain showed no effect of social gain for either type of SWR (n = 40, P > 0.05). g, Histology of CA3-implanted Grik-4 animals, previously injected with Cre-dependent AAV expressing ChR2–eYFP (green). h, Close-up view of the CA3 area. i, Examples of spontaneous and optogenetically triggered ripples in CA3. White lines are LFPs from CA2; colour maps show wavelet spectrograms; dashed lines demarcate the period of illumination. j, LFPs showing ripple activity in CA1 and CA3 but not CA2 after optogenetic triggering of ripples in CA3. k, The rate of events in sessions with CA3-triggered ripples was significantly higher than in non-stimulated sessions (P < 0.003), with no significant difference compared with the rate of ripples in response to CA2-triggered ripples (P > 0.05). l, The participation probability (the fraction of ripples in which a neuron fires at least one spike) of all pyramidal cells during spontaneous versus triggered CA2 ripples was highly correlated (CA1, n = 96, r = 0.66, P < 7 × 10−10, Pearson’s correlation; CA2, n = 67, r = 0.34, P < 3 × 10−22; CA3, n = 112, r = 0.67, P = 3 × 10−15). m, A similar result was obtained by comparing firing rates (CA1, r = 0.59, P < 2 × 10−7; CA2, r = 0.49, P < 1.7 × 10−5; CA3, r = 0.66, P < 8 × 10−10). n, The firing-rate gain (in-ripple firing rate divided by baseline firing rate) showed similar tendencies (CA1, r = 0.63, P < 1.6 × 10−12; CA2, r = 0.47, P < 2.1 × 10−3; CA3, r = 0.71, P < 1.7 × 10−18).
