Submitted on November 13, 2008
Revised on January 23, 2009
Accepted on February 16, 2009
Modulation of low frequency induced synaptic depression in the developing CA3-CA1 hippocampal synapses by NMDA and metabotropic glutamate receptor activation
Joakim Strandberg1*, Pontus Tobias Wasling2, and Bengt Gustafsson
1 Sahlgrenska Academy
2 Physiology and Pharmacology
* To whom correspondence should be addressed. E-mail: joakim.strandberg{at}physiol.gu.se.
Brief test pulse stimulation (0.2-0.05 Hz) of naïve (previously non-stimulated) developing hippocampal CA3-CA1 synapses leads to a substantial synaptic depression, explained by AMPA (
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) silencing. Using field recordings in hippocampal slices from P8-P12 rats we examined this depression of naïve synapses using more prolonged test pulse stimulation as well as LFS (low frequency (1 Hz) stimulation). We found that 900 stimuli produced depression during stimulation to about 40 % of the naïve level independent of whether test pulse stimulation or LFS was used. This result was also observed during combined blockade of NMDAR/mGluRs (N-methyl-D-aspartate/metabotropic glutamate receptors) although the depression was smaller (to about 55 % of naïve 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, test pulse stimulation produced as much depression as LFS when applied to naïve synapses even when allowing for NMDAR and mGluR activation. Our results seem in line with the notion that NMDA and mGlu receptors may exert a bidirectional control on AMPA receptor recruitment to synapses.
