Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats

Figure 1

Early inhibition/capturing of DNMT impairs LTP maintenance. (a) L-LTP was induced using theta burst stimulation (TBS), which consisted of four theta epochs delivered at 0.1 Hz. Each epoch, in turn, consisted of 10 trains of four pulses (at 100 Hz) that were delivered at 5 Hz. (b) The field excitatory postsynaptic potential (fEPSP) slope was normalized to the average value during the 20 min before TBS in each experiment. Hippocampal slices were exposed to a 5AZA or vehicle (gray bar) 20 min after tetanization. Less L-LTP was induced by TBS in slices that were treated with 5AZA (25 μM; open circles) than in slices treated with vehicle (0.001% CH3COOH; closed circles). Inset: representative fEPSPs are shown before (gray line) and at 120 min after (black line) LTP induction. (c) Hippocampal slices were exposed to either a 5AZA or vehicle (gray bar). In the absence of LTP induction, synaptic efficacy was not affected by either 5AZA (25 μM; open square) or vehicle (0.001% CH3COOH; closed square). Inset: representative traces are shown before (gray line) and at 60 min after (black line) initial exposure to 5AZA or vehicle. For all panels, the calibration bar indicates 1 mV and 5 ms; the error bars indicate the SE and numbers in parentheses corresponds to the number of animals and number of slices.

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