Selective dynamin 1 inhibition through siRNA impairs both synaptic plasticity and associative memory.

<p><b>A</b>, siRNA specific for murine dynamin 1 reduces protein expression. An example of western blot showing that Penetratin 1- conjugated dynamin 1 siRNA reduces protein expression. Cells are lysed 48 hours after the treatment with siRNA. Dynamin 1 is detected using a rabbit polyclonal anti-dynamin1 antibody. Penetratin 1- conjugated Control siRNA, that does not affect dynamin 1 expression, does not change protein levels. n = 3 for each group. <b>B</b>, Penetratin 1- conjugated dynamin 1 siRNA (open bars) (80 nM in a final volume of 1.5 μl over 1 minute, bilateral injections twice a day for 3 days) impairs contextual fear memory compared to control siRNA infused mice (grey bars) (Mann-Whitney U_{150, 126} = 21.00, <i>p</i> = 0.0089). Moreover, control siRNA infused mice show similar amount of freezing as vehicle-infused animals (black bars). <b>C</b>, Penetratin 1- conjugated dynamin 1 siRNA (open bars) does not modify cued fear memory compared to Penetratin 1- conjugated Control siRNA (grey bars) (Mann-Whitney U_{99, 90} = 44.50, <i>p</i> = 1.00) in mice previously tested for contextual fear conditioning at 24 hours after the shock. <b>D</b>, Bilateral infusions of Penetratin 1- conjugated dynamin 1 siRNA (open triangles) (80 nM in a final volume of 1.5 μl over 1 minute, repeated 2 times a day for three days) into dorsal hippocampi decrease LTP compared to Penetratin 1- conjugated Control siRNA treatment (grey squares) (F_1,9 = 5.578, <i>p</i> = 0.001). As an internal control, slices from vehicle-infused animals (black circles) show similar amounts of potentiation as those from Penetratin 1- conjugated Control siRNA treated animals. Error bars indicate SEM.