Abstracts

Rationale: Abnormalities of ?-aminobutyric acid (GABA)-mediated inhibition prominently contribute to epileptogenesis. In the rat undercut (UC) model of posttraumatic epileptogenesis, defects of inhibition are indicated by decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal neurons of sensorimotor cortex. Furthermore immunohistochemical experiments show decreases in somatically-targeting inhibitory axonal terminals. To evaluate the functional defects of somatic inhibition mediated by fast-spiking (FS) interneuons, we quantified unitary IPSCs in excitatory regular-spiking (RS) cells generated by FS interneurons, estimated the quantal size at FS-to-RS synapses, and quantified axonal bouton density of FS interneurons.Methods: Undercut surgery was performed in P21 male S-D rats. After at least two weeks of recovery, paired whole-cell recordings were performed between FS and RS cells in layer IV of somatosensory cortex of injured and na ve rats. Unitary (u-) IPSCs were evoked in RS cells by escape action potentials from voltage-clamped FS cells. Multiple synaptic parameters were quantified (see Results). In addition, asynchronous synaptic release from FS cells in strontium-containing ACSF was evoked to estimate the quantal size. FS cells were filled with biocytin to assess their axonal bouton density.Results: 1) Synaptic failures occurred in 25 of 26 FS-RS UC pairs (failure rate, 0.28 0.04, n = 25 pairs), but in only 2 of 21 control pairs (failure rate, 0.14 0.07, n = 2 pairs). 2) Synaptic strength (including synaptic failures) of uIPSCs in UC cortex (35.4 5.4 pA, n = 26) was markedly reduced to 14% of control (245.6 34.0 pA, n = 21, P < 0.001). 3) Similarly, the synaptic potency of uIPSCs in UC cortex (excluding synaptic failures) (45.1 5.4 pA, n = 26) was decreased to 18% of control (246.9 33.7 pA, n = 21, P < 0.001). 4) Coefficient of variation of uIPSCs was significantly increased in UC pairs (0.47 0.03, n = 26) compared to control (0.29 0.03, n = 21, P < 0.001). 5) The paired pulse ratio of uIPSCs in UC slices was significantly increased (0.92 0.03, n = 24 in UC vs. 0.84 0.02, n = 0.21 in control; P < 0.05). 6) Kinetics of uIPSCs were not significantly altered in RS cells of UC cortex vs. controls. 7) Measurements of presumed quantal events during asynchronous synaptic release showed that there was no significant difference in quantal size between UC postsynaptic RS cells (17.7 3.4 pA, n = 5 pairs) compared to control RS cells (23.4 3.4 pA, n = 5 pairs) (P = 0.28). 8) Axonal bouton count in biocytin-filled FS cells showed that these neurons had significantly lower bouton density (0.85 0.04 / m, n = 4 cells), compared to control cells (1.02 0.05 / m, n = 4 cells) (P < 0.05).Conclusions: Conclusions: Marked disinhibition is present in layer IV of somatosensory cortex in the undercut model, which is due to decreased release probability, and a likely contribution from a reduced number of functional synapses. (This work was supported by grants NS012151 and NS039579 from NINDS).