Supplementary data for: Graphene Microelectrode Arrays, 4D Structured Illumination Microscopy, and a Machine Learning Spike Sorting Algorithm Permit the Analysis of Ultrastructural Neuronal Changes During Neuronal Signalling in a Model of Niemann-Pick Disease Type C

Supplementary example data for the work presented in "Graphene Microelectrode Arrays, 4D Structured Illumination Microscopy, and a Machine Learning Spike Sorting Algorithm Permit the Analysis of Ultrastructural Neuronal Changes During Neuronal Signalling in a Model of Niemann-Pick Disease Type C". 

Abstract: 

Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing our understanding of the basis of neuronal functions. However, the rapid millisecond-scale fluctuations in neuronal activity and the subtle sub-diffraction resolution changes of synaptic morphology pose significant challenges to this endeavour. Here, we use specially designed graphene microelectrode arrays (G-MEAs), which are compatible with high spatial resolution imaging across various scales as well as permit high temporal resolution electrophysiological recordings to address these challenges. Furthermore, alongside G-MEAs, we have developed an easy-to-implement machine learning algorithm to efficiently process the large datasets collected from MEA recordings. We demonstrate that the combined use of G-MEAs, machine learning (ML) spike analysis, and four-dimensional (4D) structured illumination microscopy (SIM) enables monitoring the impact of disease progression on hippocampal neurons which have been treated with an intracellular cholesterol transport inhibitor mimicking Niemann-Pick disease type C (NPC), and show that synaptic boutons, compared to untreated controls, significantly increase in size, leading to a loss in neuronal signalling capacity.