Fig 1: Demyelination decreases connectivity, reliability, and rapid facilitation of parvalbumin-positive (PV+) unitary inhibitory postsynaptic currents (uIPSCs).(a) Immunofluorescence image of a connected control PV+ basket cell (BC) (red) and layer 5 (L5) pyramidal neuron (PN) (white). (b) Example traces of 10 single-trial uIPSC traces (gray) overlaid with mean average (>60 trials, black). Inset: uIPSCs abolished by gabazine (GABAA blocker, 4 µM). (c) Cuprizone-treated mice show significantly lower connection probability between PV+ BC and L5-PN (chi-square test *p=0.0182, n = 78 pairs). (d) Example fits (blue) of uIPSCs for rise- and decay time, amplitude, failure rate, amplitude, and latency analyses (d, AP to 10% uIPSC peak amplitude). (e) Cuprizone increased failures by fivefold and the average peak amplitude by ~2.5-fold (Mann–Whitney test **p=0.012) and (f) reduces the mean amplitude (Mann–Whitney test *p=0.0256). (g) uIPSCs latency remained unchanged (Mann–Whitney test n.s., p>0.999). (h) Cuprizone impairs short-term facilitation. Dotted line indicates expected amplitude for uIPSC2 (scaled from uIPSC1). (i) Left: confocal z-projected image of a control PV+ axon (red) immunostained with Syt2 (green). Right: surface-rendered 3D image of the same axon. (j) Example sections of 3D reconstructions. (k) Cuprizone increased the Syt2+ puncta spacing by approximately twofold (Mann–Whitney test ****p<0.0001, n = 12). Data shown as mean ± SEM and open circles individual axons or pairs. n.s., not significant.