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

Strandberg J, Wasling P, Gustafsson B. Modulation of low-frequency-induced synaptic depression in the developing CA3-CA1 hippocampal synapses by NMDA and metabotropic glutamate receptor activation. J Neurophysiol 101: 2252-2262, 2009. First published February 18, 2009; doi:10.1152/jn.91210.2008. 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 alpha-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 similar 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 similar to 55% of nave 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 even than that observed during combined blockade. We also found that mGluR blockade alone facilitated the LFS-induced depression. In conclusion, testipulse stimulation produced as much depression as LFS when applied to na ve synapses even when allowing for NMDAR and mGluR activation. Our results seem in line with the notion that NMDARs and mGluRs may exert a bidirectional control on AMPA receptor recruitment to synapses.