Figure 7: Fos ecRNA is induced by behavioural experience and modulates memory formation.
From: Extra-coding RNAs regulate neuronal DNA methylation dynamics
(a) Contextual fear conditioning is associated with increased Fos mRNA and Fos ecRNA in the CA1 subregion of the hippocampus, as compared with experimentally naïve controls (N=naïve, FC=fear conditioned; n=16 per group; Mann—Whitney U test, U=15 and P<0.0001 for Fos mRNA, U=73 and P=0.038 for Fos ecRNA). Area CA1 was subdissected from total hippocampus 1 h following contextual fear conditioning. (b) Experimental timeline for Fos ecRNA ASO experiments in vivo. (c) Fos ecRNA ASO treatment decreased Fos ecRNA expression in the CA1 of the hippocampus (n=8–9 per group, unpaired Student’s t-test, t15=2.173, P=0.0462). (d) Top, contextual fear conditioning design. Bottom, Fos ecRNA ASO treatment impaired long-term memory but did not alter baseline freezing or short-term memory (n=8–9 per group; STM unpaired Student’s t-test, t15=1.245, P=0.23; LTM unpaired Student’s t-test, t15=2.640, P=0.0186). (e) Open field test. Top, representative traces showing animal location during 30 min test session. Fos ecRNA knockdown did not affect total distance travelled (bottom left; unpaired Student’s t-test, t14=1.517, P=0.1514) or time spent in the center of an open field test (bottom right; unpaired Student’s t-test, t14=0.005, P=0.99; n=8 per group). All data are expressed as mean±s.e.m. Individual comparisons, *P<0.05 and ****P<0.0001.
