Extended Data Fig. 4: Blocking long-term potentiation during memory consolidation impairs recall, and neuronal population-based analysis yields dynamic and selective engrams.

a-i, Simulation with blockage of long-term potentiation (LTP) during consolidation. a, Schematic of simulation protocol with blockage of long-term potentiation (LTP) during consolidation. LTP induced by triplet STDP and transmitter-induced plasticity are both blocked. Network and simulation parameters as in Fig. 1b except that A = δ = 0 during consolidation (see Methods). b-d, Post-encoding evolution of engram cells in a. Means and 99% confidence intervals are shown. n = 10 trials. b, Engram cell ensemble as a fraction of all neurons. Dashed line indicates engram cell ensemble at the end of training. c, Ensemble overlap between probing-activated engram cells at consolidation time = t and t-1 h as a fraction of engram cells at consolidation time = t-1 h. Dashed line indicates ensemble of neurons that remained part of the engram in all sampled time points (that is, consolidation time = 0, 1, …, 24 h) as a fraction of engram cells at consolidation time = 0 h (that is, training-activated engram cells). d, Ensemble overlap between engram cells activated during both probing and training as a fraction of training-activated engram cells (top), probing-activated engram cells (middle) and all neurons in the network (bottom). e-g, Analysis of memory recall in a. Means and 99% confidence intervals are shown. n = 10 trials. Color denotes stimulus as in Fig. 1c. e, Firing rate of engram cells averaged across all cue presentations during recall as a function of consolidation time. Dashed line indicates threshold ζ^thr = 10 Hz for engram cell activation. f, Memory recall as a function of consolidation time. g, Discrimination index between recall evoked by cues of the training stimulus and individual novel stimuli as a function of consolidation time. h, Mean weight strength of plastic synapses in the network in a clustered according to engram cell status. Top, feedforward excitatory synapses onto excitatory neurons. Middle, recurrent excitatory synapses onto excitatory neurons. Bottom, recurrent inhibitory synapses onto excitatory neurons. Left, at the end of the training phase. Right, after 24 h of consolidation. Representative trial is shown. i, Memory recall evoked by cues of the training stimulus at t_{consolidation} = 24 h in Fig. 1i (control) and in f (LTP blockage) (same data). Two-sided Wilcoxon signed-rank test, W = 0.0, P = 0.001953. Means and standard deviations are shown. n = 10 trials per group. *P < 0.05. j-o, Analysis of engram dynamics in Fig. 1b using non-negative matrix factorization to identify engram cells (see Methods). Means and 99% confidence intervals are shown. n = 10 trials. j, Post-encoding evolution of engram cells. Ensemble overlap between engram cells activated during both probing and training as a fraction of training-activated engram cells (left), probing-activated engram cells (middle) and all neurons in the network (right). k, Ensemble of engram cells as a fraction of all neurons. Dashed line indicates engram cell ensemble at the end of training. l, Ensemble overlap between probing-activated engram cells at consolidation time = t and t-1 h as a fraction of engram cells at consolidation time = t-1 h. Dashed line indicates ensemble of neurons that remained part of the engram in all sampled time points (that is, consolidation time = 0, 1, …, 24 h) as a fraction of engram cells at consolidation time = 0 h (that is, training-activated engram cells). Note that the dashed line is close to 0. m-o, Color denotes stimulus as in Fig. 1c. m, Firing rate of engram cells averaged across all cue presentations during recall as a function of consolidation time. Dashed line indicates threshold ζ^thr = 10 Hz for engram cell activation. n, Memory recall as a function of consolidation time. o, Discrimination index between recall evoked by cues of the training stimulus and individual novel stimuli as a function of consolidation time.