Figure 2.
Arc antisense infusion 2 h after high-frequency stimulation blocks LTP consolidation. Time course plots show changes in the medial perforant path-evoked fEPSP slope expressed in percentage of baseline. Values are means ± SEM. HFS is indicated by the arrow. Infusion of Arc AS- and SC-ODN are indicated by filled and open bars, respectively. A, Top, LTP maintenance was rapidly and persistently inhibited after local infusion (1 μl, 0.5 mm, 12.5 min) of Arc AS-ODN at 2 h after HFS. Bottom, Averaged field potentials traces (4 sweeps) collected at the end of baseline recording (Baseline), immediately before AS infusion (Post-HFS), and at the end of recording (Post-AS). Calibration: 5 mV, 2 ms. B, Arc AS-ODN infusion 4 h after HFS had no effect on LTP maintenance. C, Infusion of SC Arc ODN 2 h after HFS had no effect on LTP maintenance. D, Arc AS infusion had no effect on basal synaptic efficacy. E, Infusion of a second AS sequence (AS2) targeting a nonoverlapping region of the Arc mRNA similarly reversed ongoing LTP (n = 5). F, Magnitude of fEPSP slope changes. n = 5–8 in all groups. *p < 0.05, significantly different from baseline. G, LTP reversal is coupled to specific knockdown of Arc protein. Quantification of Western blots from dentate gyrus homogenates. Tissue was collected at the end of the experiments shown in A and C. Expression of Arc, but not β-actin, α-CaMKII, or PSD-95, were significantly reduced in AS-treated rats (*p < 0.05). Representative immunoblots: + indicates infused dentate gyrus, and − indicates contralateral, non-infused dentate gyrus.