Synaptic Plasticity at the Schaffer Collateral-CA1 Pathway

In vivo field excitatory postsynaptic potentials (fEPSPs) in the pyramidal layer of the hippocampal CA1 region were recorded as previously explained in the Materials and methods section (An and Sun, 2017, 2018; An et al., 2019). Briefly, rats were anesthetized with isoflurane and placed in a stereotaxic frame for surgery (SN-3; Narishige, Japan). Core body temperature was monitored throughout the experiment, and a heating pad was used to maintain the temperature of the animals at 36.5 ± 0.5°C. The scalp was opened, and small holes were drilled in the skull using a trephine for the monopolar recording (insulated platinum iridium wire; AM Systems; AP: −3.3 mm, ML: ± 2.3 mm, DV: 2.6–2.8 mm) and tungsten bipolar stimulating electrodes (FHC; ME; hippocampal Schaffer collaterals region; AP: −4.0 mm, ML: ± 3.3 mm, DV: −2.2 to −3.0 mm). The head side of each rat was chosen randomly but counterbalance among groups. After the electrodes were lowered and located properly in desired positions, input/output (I/O) curves and paired-pulse facilitation (PPF) were assessed. The frequency of test pulse recording ranged from 30 to 60 s. A baseline recording was re-established for approximately 5–10 min following the completion of each recording. Low-frequency stimulation (LFS) (900 pulses of 1 Hz) was delivered to induce long-term depression (LTD). The stimuli were delivered every minute at an intensity that evoked a response of 60–70% of the maximum response, which was obtained from the I/O recording. Since LTD should last for at least hours, the expression of LTD in the current study can only be defined as a short-lasting long-term depression (SL-LTD). Initial data measurement was performed in Clampfit 9.0 (Molecular Devices, Sunnyvale, CA, United States). The fEPSPs slope was used to measure synaptic efficacy. The average amplitudes during the baseline period were normalized to 100%, and the relative amplitudes at every point were normalized relative to the baseline period. The average amplitude between 41 and 60 min after the completion of the LFS was used to analyze.