Fig. 1: Neuronal ensemble-specific Dnmt3a2 overexpression enhances fear memory.
From: Neuronal ensemble-specific DNA methylation strengthens engram stability
a Schematic representation of the viral constructs used for neuronal ensemble targeted gene manipulation. E-SARE promoter drives the expression of HA-GFP, HA-LacZ or HA-Dnmt3a2. Constitutive tDimer expression (human Synapsin promoter) serves as an infection marker. b Correlation analysis of 5mC and HA immunocytochemical signal intensities in primary hippocampal cultures. Cultures were infected with E-SARE-HA-GFP (n = 4 independent cell preparations, Pearson’s r = 0.0035, p = 0.9756) or E-SARE-HA-Dnmt3a2 (n = 4 independent cell preparations, Pearson’s r = 0.5174, p < 0.0001). c Experimental schedule used to assess the effect of Dnmt3a2 overexpression in the neuronal ensembles in contextual fear memory. Graph represents % time freezing in the conditioned context. Mice were injected with E-SARE-HA-GFP or E-SARE-HA-Dnmt3a2 viruses (E-SARE-HA-GFP (n = 16) vs E-SARE-HA-Dnmt3a2 (n = 13), t(27) = 2.083, p = 0.0468 by unpaired t-test). d Experimental schedule used to assess the effect of Dnmt3a2 overexpression in the neuronal ensembles in freezing in an altered context. Graph represents % time mice spent freezing in the altered context. Mice were injected with E-SARE-HA-GFP or E-SARE-HA-Dnmt3a2 viruses (E-SARE-HA-LacZ (n = 7) vs E-SARE-HA-Dnmt3a2 (n = 7), t(12) = 0.06332, p = 0.9506 by unpaired t-test). ITR: inverted terminal repeat, w- week, DG: Dentate gyrus of the hippocampus, CFC: contextual fear conditioning, rAAVs: recombinant adeno-associated viruses. *p < 0.05; ****p < 0.0001, ns: not significant by the respective statistical test. Error bars represent s.e.m. Source data are provided as a Source Data file.
