Fig. 6: Phospho-deficient S129A αS reduces the excitatory/inhibitory balance in rat SNCA−/− hippocampal neurons.
From: Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity
a Spontaneous excitatory (sEPSC) and inhibitory postsynaptic currents (sIPSC) measured in DIV14-18 hippocampal neurons from SNCA−/− rats transduced with αS WT or αS S129A (schematics created with BioRender.com). b Representative sEPSC traces. c Representative sIPSC traces. Scale bars, X-axis = 1 s and Y-axis = 100 pA. d sEPSC frequency in SNCA−/− neurons expressing WT αS or αS S129A. e Cumulative frequency distribution of data shown in d, expressed as percentage. f sEPSC amplitude in SNCA−/− neurons expressing αS WT or αS S129A. g Cumulative frequency distribution plot of data shown in f, expressed as percentage. Total number of individual events analyzed in panels e and g: αS WT = 1228; αS S129A = 1701. Total number of individual cells across two independent neuronal cultures (N = 2) recorded in sEPSC experiments: WT αS = 21 and αS S129A n = 12. h, i sIPSC frequency between conditions as bar charts and cumulative distribution, respectively. j sIPSC amplitude in SNCA−/− neurons expressing WT or S129A αS. k Cumulative frequency distribution of data shown in j. Total number of individual events analyzed in panels i and k: αS WT = 302; αS S129A = 585. Total number of individual cells across two independent neuronal cultures recorded in sIPSC experiments: αS WT = 19 and αS S129A = 15. l, m The excitatory/inhibitory ratio of the amplitude as a bar chart and cumulative frequency distribution, respectively. E/I amplitude ratios were derived from f and j. Respective averages in f (αS WT or αS S129A) were divided by respective individual values (αS WT or αS S129A) in j to obtain E/I amplitude ratios. Each circle represents an individual cell. Recordings performed on at least three different days. Unpaired t-tests with Welch’s correction; two-tailed; mean ± SD; ns not significant; ***p < 0.001; ****p < 0.0001.
