Mapping and Deciphering Neural Codes of NMDA Receptor-Dependent Fear Memory Engrams in the Hippocampus
(A) The intertwined memory trace retrievals (defined as retrievals between individually distinct memory traces, see underlined brackets) and alternating retrieval dynamics (defined as retrievals between distinct simple traces, upper brackets) were prevalent in all five control mice during the 5-min contextual recall. Symbols: CS trace, blue triangle; US trace, red triangle; US-to-CS associative trace, red diamond; CS-to-US associative trace, blue diamond. The intertwined retrievals between different traces within 7 sec time window are underlined, whereas alternating retrievals between US and CS or CS and US are marked by upper brackets. (B) Degraded memory codes in five mutant mice during 5-min contextual retention tests. Only KO #1 had five associative traces during the recall, all other mutants failed to produce such traces. Intertwined and alternating retrieval patterns were greatly diminished. (C) The intertwined memory retrieval in the control group (blue plots) during contextual recall follows an exponential decay process, indicating that intertwined memory traces were recalled in temporal clusters. The mutant mice were significantly impaired in the temporal association between recalled memory traces (Red plots) (two-sample Kolmogorov-Smirnov test, p = 0.014). (D) Significant differences in the average occurrences of intertwined memory trace pairs between the control and knockout mice (Wilcoxon rank sum test, **p<0.01; error bars represent SD). (E) Numbers of various temporal structures of memory traces in single, doublet, triplet across the control and mutant mice during contextual recall. (F) The alternating retrieval for US simple trace followed with a simple CS memory trace or CS simple trace followed by a US memory trace in the control mice also exhibited exponential decay distribution, but not in the mutant mice (two-sample Kolmogorov-Smirnov test, p = 0.0042). Trace interval for 50% temporally associational recall in the control is 3.6 sec for control mice and 8.2 sec for mutant mice. (G) Differences in the alternating retrieval rates between the control and knockout mice (Wilcoxon rank sum test, **p<0.01; error bars represent SD). To appreciate temporal associativeness of memory recalled, memory patterns from a control (Mouse #4) and mutant mouse (Mouse #3) were converted into audio clips of “Pavlovian memory symphony” (Sound S1 and S2 correspondingly).