Figure 1. Low-frequency stimulation induces input-selective and reversible long-term depression at CA3-to-CA1 synapses in vivo.
(a,b) Application of strong LFS (horizontal bar, LFS-900; 900 pulses at 1 Hz) induced robust and stable LTD. Three hours after LTD induction, application of high-frequency stimulation (arrow, HFS; 200 Hz) induced potentiation of synaptic transmission such that LTD was completely reversed. As summarized in (b), the EPSP decreased to 74.2±3.9%, at 3 h post LFS (3 h), n=5, P<0.05 compared with pre-LFS baseline (Pre); one-way ANOVA-Tukey. At 1 h post HFS (4 h) the EPSP reverted to 99.1±3.7%, n=5, P>0.05 compared with Pre; P<0.05 compared with LFS). (c,d) In four animals, two stimulation electrodes (S1, black and S2, purple) were implanted in different locations in the stratum radiatum to allow independent activation of the Schaffer collateral-commissural pathway. One hour after stable baseline recording from both S1 and S2 pathways, application of LFS-900 to S1 induced LTD in the S1 pathway but not in the S2 pathway. Conversely, 1 h after the first LFS, a second LFS was applied to S2 pathway that only induced LTD in pathway S2. As summarized in (d) One hour after application of LFS1, the EPSP in pathway S1 decreased to 67.4±5.6% (P<0.05 compared with Pre; one-way ANOVA-Tukey) but did not change significantly in the S2 pathway (103.6±4.5%, P>0.05 compared with Pre; P<0.05 compared with S1 pathway; t-test). In contrast, 1 h after application of LFS2, the EPSP was significantly reduced in the S2 pathway (61.1±10.4%, P<0.05 compared with Pre) but no further change was seen in the S1 pathway (75.4±4.1%, P>0.05 compared with EPSP amplitude pre-LFS2). Values are expressed as % mean baseline EPSP amplitude±s.e.m. Insets show representative EPSP traces at the times indicated. Calibration bars: vertical, 2 mV; horizontal, 10 ms. *P<0.05.
