Fig. 6: Transporter inhibition drives extrasynaptic diffusion of serotonin.
From: Coding principles and mechanisms of serotonergic transmission modes
A 3D spatiotemporal profiling of electrically evoked fluorescence ΔF/F0 responses before (left) and after (right) the bath application of 10 µm escitalopram (ECIT). B Pixel-wise maximal ΔF/F0 plots before (left) and after (right) the bath application of ECIT at the same isolated release site indicated by the pink arrows in A. C Averaged spatial spread length constants (Ctrl: 0.72 ± 0.03 µm; ECIT: 0.84 ± 0.04 µm, Z = 2.67, p = 0.007, n = 17 releasing synapses from 5 animals). D 3D profiling of ΔF/F0 responses at isolated releasing synapses before and after the bath application of ECIT. Note serotonin leaking out of synapses via 1 − 3 outlets after the bath application of ECIT (1.53 ± 0.17; n = 17 releasing synapses from 5 animals). Scale bar applied to all in D. E Minor (Ctrl: 0.93 ± 0.05 µm; ECIT: 0.98 ± 0.05 µm; Z = 0.59, p = 0.58, n = 17 releasing synapses from 5 animals) and major (Ctrl: 1.31 ± 0.10 µm; ECIT: 2.32 ± 0.16 µm; Z = 3.62, p < 0.001, n = 17 releasing synapses from 5 animals) full width at half maximums (FWHMs) of serotonin diffusion profiles at isolated releasing synapses before and after the bath application of ECIT. F Aspect ratio (Ctrl: 1.30 ± 0.06; ECIT: 2.02 ± 0.11; Z = 3.48, p < 0.001, n = 17 releasing synapses from 5 animals) and roundness (Ctrl: 0.79 ± 0.03; ECIT: 0.52 ± 0.03; Z = −3.53, p < 0.001, n = 17 releasing synapses from 5 animals) values of serotonin diffusion profiles at isolated releasing synapses before and after the bath application of ECIT. G Plots of pixel-wise maximal ΔF/F0 before (green) and after (red) the bath application of ECIT and their difference (cyan; ECIT-Ctrl). H Relative integration values of ΔF/F0 at distance of 0.5 µm (Ctrl: 0.37 ± 0.003; ECIT: 0.38 ± 0.003; Z = 1.34, p = 0.19, n = 17 releasing synapses from 5 animals), 0.5 − 3 µm (Ctrl: 0.49 ± 0.04; ECIT: 0.71 ± 0.05; Z = 2.91, p = 0.002, n = 17 releasing synapses from 5 animals), and 3 − 8 µm (Ctrl: 0.27 ± 0.04; ECIT: 0.38 ± 0.06; Z = 1.91, p = 0.06, n = 17 releasing synapses from 5 animals). Asterisks indicate p < 0.05 (Wilcoxon tests).
