Modulation of Low-Frequency-Induced Synaptic Depression in the Developing CA3–CA1 Hippocampal Synapses by NMDA and Metabotropic Glutamate Receptor Activation

Brief test-pulse stimulation (0.2–0.05 Hz) of naive (previously nonstimulated) developing hippocampal CA3–CA1 synapses leads to a substantial synaptic depression, explained by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silencing. Using field recordings in hippocampal slices from P8 to P12 rats, we examined this depression of naive synapses using more prolonged test-pulse stimulation as well as low-frequency (1 Hz) stimulation (LFS). We found that 900 stimuli produced depression during stimulation to ∼40% of the naive level independent of whether test-pulse stimulation or LFS was used. This result was also observed during combined blockade of N-methyl-d-aspartate/metabotropic glutamate receptors (NMDAR/mGluRs) although the depression was smaller (to ∼55% of naive level). Using separate blockade of either NMDARs or mGluRs, we found that this impairment of the depression resulted from the NMDAR, and not from the mGluR, blockade. In fact, during NMDAR blockade alone, depression was smaller ev...