Abstracts

Rationale: The frequency of miniature inhibitory postsynaptic currents (mIPSCs) is reduced in layer V pyramidal (P) cells of sensorimotor cortical slices in the rat “undercut (UC)” model of posttraumatic epileptogenesis, associated with structural abnormalities in inhibitory axons of fast-spiking (FS) interneurons. To assess alterations in presynaptic terminal function that might underlie decreased GABAergic inhibition in this model, we examined unitary (u) IPSCs evoked by FS cells at 3 postsynaptic targets. Methods: We obtained paired whole-cell recordings from FS interneurons and postsynaptic cells in layer IV barrel cortex of 5-6 wk-old naïve rats and UC rats 3 weeks after the partial isolation. uIPSCs were evoked in voltage clamped postsynaptic cells by single or trains of action potentials in FS cells. The amplitude, failure rate, coefficient of variation (C.V.), paired-pulse ratio (PPR) and 10-90% decay time of evoked uIPSCs were assessed. Data are presented as mean±s.d.. Results: Three groups of uIPSCs were recorded: (A) autaptic (aut-) uIPSCs (FS cells onto themselves); (B) FS-FS cell uIPSCs and (C) FS to excitatory regular-spiking (RS) cell uIPSCs. 1) Peak uIPSCs amplitudes in cells from UC were smaller than in controls (aut-:141.1±122.2 pA, n=9 vs. 414.3±159.2 pA in control, n=14, p<0.01; FS-FS, 92.6±59.2 pA, n=10 vs. 260.2±159.6 pA control, n=7, p<0.05; and FS-RS, 17.7±12.5 pA, n=4 vs. 350.6±213.8 pA control, n=7, p<0.01). 2) There were no uIPSC failures in naïve controls. Failure rates in UC slices were 0.11±0.18 (n=10) and 0.41±0.08 (n=4) for FS-FS and FS-RS connections, respectively. 3) C.V. of uIPSCs was larger in UC animals vs. controls (aut-, 0.26±0.10, n=9 vs. 0.16±0.04 control, n=13, p<0.05; FS-FS, 0.36±0.07, n=10 vs. 0.24±0.08 control, n=7, p<0.01; and FS-RS, 0.48±0.22, n=4 vs. 0.25±0.13, n=7, p=0.12). 4) Paired pulse ratio was variable and no significant change was present in any group, although there was a trend towards higher values in UC compared to naïve ones (aut-, 0.91±0.04, n=3 vs. 0.85±0.09 control, n=10, p=0.11; FS-FS, 0.91±0.27, n=10 vs. 0.78±0.07, n=7 control, p=0.18; FS-RS, 0.88±0.22, n=4 vs. 0.76±0.04 control, n=7, p=0.36). All naïve control uIPSCs exhibited paired pulse depression and paired pulse facilitation was present in some pairs from UC animals. 5) There were no significant differences in 10-90% decay times for uIPSCs for any group). Conclusions: Inhibition evoked by FS interneurons onto themselves, and onto other FS interneurons and excitatory neurons is compromised in the undercut model. Increased failure rates, larger CV, as well as higher PPR in some connections in UC animals suggest that abnormalities in inhibitory presynaptic terminals are present and contribute to disinhibition and epileptogenesis.