Fig. 4: Emx1-Cre;Irsp53fl/fl LH-GABA neurons show increased excitatory synaptic transmission but decreased excitability.
From: The PFC-LH-VTA pathway contributes to social deficits in IRSp53-mutant mice
a–c Increased mEPSC frequency but not amplitude in LH-GABA neurons in Emx1-Cre;Irsp53fl/fl mice (8 weeks). (n = 11 neurons from 3 mice [WT], 14, 4 [cKO], Student’s t test). d–f Normal mIPSC frequency and amplitude in Emx1-Cre;Irsp53fl/fl LH-GABA neurons (8 weeks). (n = 12, 3 [WT], 14, 4 [cKO], Student’s t test). g Strategy to measure optogenetically evoked excitatory postsynaptic currents (oEPSCs) in LH-GABA neurons receiving mPFC inputs. AAV-CamKIIa-hChR2-EYFP was injected into the mPFC of Emx1-Cre;Irsp53fl/fl or WT (Irsp53fl/fl) mice, and AAV (PHP.eB)-mDlx-EGFP was injected into the LH to mark GABA neurons (8–12 weeks). h, i Examples of oEPSCs, which were observed in ~45% of light-stimulated LH-GABA neurons. (n = 44, 4 [WT], 57, 4 [cKO]). j Increased oEPSC amplitude in Emx1-Cre;Irsp53fl/fl LH-GABA neurons (12 weeks). (n = 20, 4 [WT], 25,4 [cKO], Student’s t test). k, l Normal input resistance in Emx1-Cre;Irsp53fl/fl LH-GABA neurons (8–12 weeks). (n = 11, 3 [WT], 12, 3 [cKO], two-way ANOVA with Sidak’s multiple comparison test). m, n Increased AP threshold in Emx1-Cre;Irsp53fl/fl LH-GABA neurons (8–12 weeks). (n = 11, 3 [WT], 12, 3 [cKO], Mann–Whitney test). o, p Normal current-firing curve of Emx1-Cre;Irsp53fl/fl LH-GABA neurons (8–12 weeks). (n = 9, 3 [WT], 12, 3 [cKO], two-way ANOVA). Significance is indicated as * (<0.05), ** (<0.01), *** (<0.001), or ns (not significant).
