Figure 1.
AED exposure disrupts IPSC development during the second postnatal week. (A) Representative confocal image of a biocytin-filled striatal medium spiny neurons (MSNs) with local dendritic arborization and spiny dendrites. Calibration bar, 30µm (B) Representative current clamp recording from a MSN, showing the characteristic repetitive, non-adapting firing pattern in response to a series of 1s hyperpolarizing and depolarizing current injections (10 pA steps) from a holding potential of −60 mV. (C) Quantification (mean±S.E.M.) of spontaneous inhibitory postsynaptic current (sIPSC) frequency at P10 and P14 showing the effect of P7 exposure to saline (control, n=28, n=32), phenobarbital (PB, 37.5 mg/kg, n=11, n=9), phenobarbital (PB, 75 mg/kg, n=9, n=23), phenytoin (PHT, 50 mg/kg, n=12, n=23), and lamotrigine (LTG, 20 mg/kg, n=11, n=11). (D) Quantification (mean±S.E.M.) of miniature inhibitory postsynaptic current (mIPSC) frequency at P10 and P14 showing effects of P7 exposure to saline (n=21, n=30), phenobarbital (37.5 mg/kg, n=6, n=6), phenobarbital (75 mg/kg, n=6, n=23), phenytoin (50 mg/kg, n=12, n=21), and lamotrigine (20 mg/kg, n=9, n=8) (E) Quantification (mean±S.E.M.) of mIPSC frequency at P18 showing effects of P7 exposure to saline (n=22), phenobarbital (37.5 mg/kg, n=6), phenobarbital (75 mg/kg, n=9), phenytoin (50 mg/kg, n=8), and lamotrigine (20 mg/kg, n=10). (F) Representative mIPSC traces from each group at P10, P14 and P18, following P7 treatment with saline, phenobarbital (75 mg/kg), phenobarbital (37.5 mg/kg), phenytoin (50 mg/kg), and lamotrigine (20 mg/kg). Data were analyzed by ANOVA with Fisher’s Least Significant Difference test for multiple comparisons. * indicates significantly different than P10 value within treatment. † Indicates significantly different than control at same age. See Supplemental Statistics Discussion for a complete discussion of ANOVA results.