Fig. 8: Heterogeneous axo-axonic synaptic plasticity underlies organized motor control.
From: An adaptive behavioral control motif mediated by cortical axo-axonic inhibition
a,b, Immunostaining of the AIS by AnkG (green) and inhibitory postsynaptic gephyrin (red) visualizes the corresponding synaptic composition (yellow) of ChC (magenta) to AIS contacts. DAPI stains nuclei (blue; n = 22 in total). c, Schematics of automated detection of ChC-innervated AISs (ChC–AISs). d, Representative examples of ChC–AIS evaluation of Pre-SSE and Post-SSE. Filled and empty arrows indicate ChC–AIS and non-ChC–AIS synapses, respectively. SSE values were classified into three subgroups (high: >1.5 for Pre-SSE, >0.6 for Post-SSE; low: <0.5 for Pre-SSE, <0.1 for Post-SSE; mid: between high and low). White triangles indicate gephyrin puncta on the AIS associated (filled) and non-associated (open) with the ChC cartridge. e–h, Examples of pre-SSE and post-SSE distribution in each slice for the experimental (learning) group and the control group (n = 10 and n = 12 for the experimental group and control group, respectively). i, Scatter plot of pre-SSEs and post-SSEs for each group. j, SSEs by the position of AISs within the cortical layer 2 for each group (n = 5 and n = 6 for the experimental group and control group). k,l, CDFs from individual mice (P = 5 × 10−5 for k and P = 2 × 10−11 for l; error bars = s.e.m., left axis) and the difference between the averages for the experimental and control conditions (experimental versus control, right axis). m,n, Probabilities by pre-SSE and post-SSE strength subgroups (high, mid and low) from individual mice. Error bars indicate s.e.m. Differences of probability distributions for pre-SSE and post-SSE (experimental versus control) (o,p) and proportional changes (experimental versus control) in the probability of each subgroup (q,r), which is confirmed by 10 independent robust random samplings (n = 3,000 each). In both SSEs, high and low subgroups were increased. The results were compared to proportional changes between unlabeled random pairs. For bootstrapping statistics (o–r), the mean and error of each bin were calculated from 10 distributions generated by independent robust random sampling (n = 3,000). For each random sampling, the probability distribution of a mouse was randomly selected from each condition (experimental and control) and used to calculate differences. Error bars indicate s.d.; P = 2.0 × 10−4 for all bins. s, Model for axo-axonic structural plasticity by heterosynaptic competition. The CDFs were tested by two-tailed two-sample Kolmogorov–Smirnov test, and the other distributions were tested by two-tailed Wilcoxon–Mann–Whitney test. Scale bars, 100 μm (a,e–h) and 5 μm (b,d). Every fluorescence image is presented by maximum intensity projection of the corresponding volumetric stack with pseudo-colors. ***P < 0.001; ****P < 0.0001; *****P < 0.00001. C, control; E, experimental; Exp., experimental.
