Fig 1: Nanoscopic Changes in Substructural Organisation of PSD95 in ALS Synapses. a Diagram of synapse subtypes, defined by the number of PSD95 nanoclusters (NCs) per PSD. PSDs can be visualised using confocal microscopy while NCs are resolved from correlative g-STED images. b Spinal cord tissue from control and SOD1G93a mice were imaged using confocal and g-STED microscopy to visualise PSDs and NCs, respectively. c Graph showing the size of the PSD95 NCs was not different between controls and SOD1G93a mice. d Graph showing the average number of NCs per PSD was significantly reduced in SOD1G93a mice. e Graph showing the number of large 3 + NC-PSDs are specifically reduced in SOD1G93a mice compared to controls. f High-resolution imaging of synapses (PSD95 and VGLUT2) and the palmitoylation enzyme, zDHHC2, was performed to investigate whether changes in zDHHC2 expression might explain the reduced number of PSD95 NCs at synapses. g Graph showing no difference in zDHHC2 puncta density between control and SOD1G93a mice. h Graph showing reduced number of PSDs expressing zDHHC2 in SOD1G93a mice