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. Author manuscript; available in PMC: 2016 Mar 18.
Published in final edited form as: Neuron. 2015 Mar 5;85(6):1257–1272. doi: 10.1016/j.neuron.2015.02.020

Figure 8. Increased susceptibility to epileptiform activity in NPTX2−/−/NPTXR−/− mice.

Figure 8

(A) Representative recordings of epileptiform activity induced following bath application of 8.5 mM [K+]o in slices from wild type mice: (i) representative trace from WT mouse showing rhythmic clusters of interictal events; (ii) two clusters of interictal events from boxed region of i on an expanded time scale; (iii) expanded time scale trace from boxed area in ii, showing rhythmicity of interictal events; (iv) single interictal event from boxed area of iii on expanded time scale. (B) Similar to A but for a representative NPTX2−/−/NPTXR−/− recording: (i) representative trace from NPTX2−/−/NPTXR−/− mouse showing rhythmic clusters of ictal events; (ii) single ictal event from boxed region in i on expanded time scale; (iii) boxed event from ii on expanded time scale with interictal events preceding the onset of an ictal event; (iv) beginning of ictal event on an expanded time scale from boxed region in iii. (C) NPTX2−/−/NPTXR−/− mice displayed significantly more ictal events during high K+ epileptiform activity (ictal events per hour, WT (n=9) vs NPTX2−/− (n=7) vs NPTXR−/− (n=7) vs NPTX2−/−/NPTXR−/− (n=11): 0.78 ± 0.39 vs 8.77 ± 6.05 vs 4.60 ± 2.48 vs 19.12 ± 4.64; H=13.85, p=0.0031, Kruskal-Wallis test with post hoc Dunn’s multiple comparisons test). (D) Interictal events in NPTX2−/−/NPTXR−/− mice were significantly less frequent (interictal event frequency, WT vs NPTX2−/− vs NPTXR−/− vs NPTX2−/−/NPTXR−/−: 0.70 ± 0.07 Hz vs 0.73 ± 0.15 Hz vs 0.35 ± 0.10 Hz vs 0.41 ± 0.04 Hz; p=0.0033, Kruskal-Wallis test with post hoc Dunn’s multiple comparisons test). (E) Representative recording from an NPTX2−/−/NPTXR−/− slice showing the effect of indiplon on high K+ induced ictal activity. Shown is a full time course of indiplon-mediated attenuation of ictal events (i) with a single ictal event prior to indiplon application (ii) and remaining interictal events (iii) after indiplon from the boxed regions in i shown on expanded time scales. (F) Bath application of indiplon significantly reduced the frequency of ictal events in NPTX2−/−/NPTXR−/− mice (ictal events per hour, baseline vs indiplon (n=6): 30.0 ± 4.3 vs 10.3 ± 5.9; p = 0.0141; Paired t test. **, p < 0.01 vs WT). Recordings throughout were performed in P15-30 mice.