Fig. 7: NMDARs cooperate with gap junctions to promote Pv neuronal burst firing. | Nature Communications

Fig. 7: NMDARs cooperate with gap junctions to promote Pv neuronal burst firing.

From: Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice

Fig. 7

a Decreased ratio of NMDAR- and AMPAR-mediated evoked EPSCs in Shank2–/– Pv neurons, compared with WT Pv neurons (prelimbic, layer 2/3, 12–13 weeks) (n = 19 neurons from 3 mice [WT] and 13/2 [KO], *p < 0.05, two-tailed Mann–Whitney test; p = 0.0125 [NMDA/AMPA ratio]). b Normal levels of mEPSCs in Shank2–/– Pv neurons, compared with WT Pv neurons (prelimbic, layer 2/3, 12–13 weeks) (n = 14/4 [WT] and 13/4 mice [KO], ns, not significant, two-tailed Student’s t-test). c D-cycloserine (DCS; 20 µM) induces increases in burst firing in WT and Shank2–/– Pv neurons neighboring a light-stimulated single Pv neuron (prelimbic, layer 2/3, 12–13 weeks), as shown by proportions of burst/tonic/no-firing neurons and mean-firing rate. Data: minimal, maximal, median, 25%, and 75% values (n = 43/18 [WT/V followed by WT/DCS] and 38/19 [KO/V followed by KO/DCS], ***p < 0.001, ns, not significant, Chi-square test [proportion], two-way ANOVA with Sidak’s test [firing rate]; p < 0.0001 [WT-proportion], p < 0.0001 [KO-proportion], interaction p = 0.0653, drug p < 0.0001, group p = 0.0003 [firing rate], WT p = 0.1654, KO p < 0.0001 [Veh-DCS, firing rate]). d Mefloquine reverses DCS-dependent enhancement of burst firing in WT and Shank2–/– Pv neurons neighboring a light-stimulated single Pv neuron (prelimbic, layer 2/3, 12–13 weeks), as shown by proportions of burst/tonic/no-firing neurons, although mean-firing rates were not changed. WT and Shank2–/– Pv neurons were recorded of firings sequentially in the presence of vehicle and DCS, followed by mefloquine (25 µM) or vehicle treatment. Data: minimal, maximal, median, 25%, and 75% values (n = 16/10 [WT-DCS-V], 27/10 [WT-DCS-MQ], 21/12 [KO-DCS-V], and 20/12 [KO-DCS-V], **p < 0.01, ***p < 0.001, Chi-square test [proportion], two-way ANOVA with Sidak/Tukey test [firing rate; see Supplementary Table 1 for details]; WT-DCS p < 0.0001, DCS-Veh p = 0.8077 [WT+DCS+Veh-proportion], WT-DCS p < 0.0001, DCS-Mef p < 0.0001 [WT+DCS+Mef-proportion], KO-DCS p < 0.0001, DCS-Veh p < 0.0001 [KO+DCS+Veh-proportion], KO-DCS p = 0.0001, DCS-Mef p < 0.0001 [KO+DCS+Mef-proportion], interaction p = 0.3942, session p = 0.0430, treatment p = 0.1332, Veh-Mef p = 0.2346 [WT-firing rate], interaction p < 0.0001, session p < 0.0001, treatment p = 0.1626, Veh-Mef p = 0.0086 [KO-firing rate]). See Source data for raw data values and Supplementary Table 1 for statistical details.

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