Abstracts

Rationale: Alterations in NMDA receptors (NMDARs) and NR2B subunit expression have been reported in the freeze-lesion model of focal cortical dysplasia. Tonic facilitation of miniature excitatory synaptic currents via presynaptic NMDARs has been observed in other epilepsy models. The present study examined whether presynaptic NMDARs were present on GABAergic terminals in the neocortex and if they were altered in cortical dysplasia.Methods: Focal freeze lesions were induced in postnatal day(PND)1 rats. Whole-cell patch-clamp recordings of 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 included in the recording pipette to block postsynaptic NMDARs.Results: D-APV (50 uM) significantly reduced the frequency of mIPSCs (66 +/- 13%; n=7)in control animals at PND12-15. Similar results were obtained with 1 uM Ro 25-6981, a NR2B subunit selective antagonist(63 +/- 12% decrease; n=6). No change in mIPSC amplitudes was observed. APV had no effect on mIPSC frequency or amplitude in PND21-25 control animals. In the PND21-25 lesion group, APV and Ro 25-6981 significantly reduced the frequency of mIPSCs (67 +/- 6%; n=7, and 65 +/- 6%; n=6, respectively)without changing amplitudes Conclusions: NR2B subunit-containing NMDARs tonically facilitate inhibitory synaptic transmission in developing rat neocortex. These presynaptic NMDARs appear to persist in freeze-lesioned animals where they may contribute to enhancing functional inhibition in this model. (NS22373)