Seena Mathew - Published Work
Altered developmental regulation of presynaptic NMDA receptors in cortical dysplasia
by S. S. MATHEW, S. J. MARKWARDT,
J. J. HABLITZ;
We have previously observed alterations in NMDA receptors (NMDARs) and NR2B subunit expression in the freeze-lesion model of focal cortical dysplasia. Tonic facilitation of miniature synaptic currents via presynaptic NMDARs has been reported in the pilocarpine model. We have examined the role of presynaptic NMDARs on GABAergic terminals in cortical dysplasia. Using whole-cell patch-clamp recordings, pharmacologically isolated IPSCs were recorded from visually identified layer II/III pyramidal cells. Recordings were obtained from control and lesioned animals at PND12-15 and PND21-25. Miniature IPSCs (mIPSCs) were recorded in the presence of TTX. MK-801 was in the recording pipette to block postsynaptic NMDARs. At PND12-15, in control animals, the competitive NMDA receptor antagonist D-APV (50 μM) significantly reduced the frequency of mIPSCs (decreased by 66 ± 13%; n=7). Similar results were obtained with the NR2B subunit selective antagonist Ro 25-6981 (1 μM)) (63 ± 12% decrease; n=6). No change in mIPSC amplitudes was observed. In PND21-25 animals, APV had no effect on mIPSC frequency or amplitude in control animals. APV and Ro 25-6981 significantly reduced the frequency of mIPSCs (67 ± 6%; n=7, and 65 ± 6%; n=6, respectively) without a change in amplitude in the PND21-25 lesioned group. These results suggest that NR2B subunit-containing NMDARs tonically facilitate inhibitory synaptic transmission in developing rat neocortex. These presynaptic NMDARs persist in freeze-lesioned animals and may contribute to continued functional inhibition in in this model.
San Diego, CA: Society for Neuroscience, 2007.
2007 Copyright by the Society for Neuroscience all rights reserved.