Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy. 2 3

47 48 Partially isolated “undercut” neocortex with intact pial circulation is a well-established 49 model of post-traumatic epileptogenesis. Results of previous experiments showed a 50 decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V 51 pyramidal (Pyr) neurons of undercuts (Li and Prince 2002). We further examined 52 possible functional abnormalities in GABAergic inhibition in rat epileptogenic 53 neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr 54 cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. 55 Compared to controls, IPSCs in Pyr neurons of injured slices showed 1) increased 56 threshold and decreased peak amplitude at threshold; 2) decreased input/output slopes; 3) 57 increased failure rates; and 4) a shift from paired pulse depression towards paired pulse 58 facilitation (increased paired pulse ratio or PPR). Increasing [Ca]o from 2 to 4mM 59 partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto 60 FS cells also had an increased PPR and failures. Blockade of GABAB receptors did not 61 affect the paired results. These findings suggest that there are functional alterations in 62 GABAergic presynaptic terminals onto both Pyr and FS cells in this model of 63 posttraumatic epileptogenesis. 64 65