SynapseCLR: Uncovering features of synapses in primary visual cortex through contrastive representation learning

3D electron microscopy (EM) connectomics image volumes are surpassing 1 mm³, providing information-dense, multi-scale visualizations of brain circuitry and necessitating scalable analysis techniques. We present SynapseCLR, a self-supervised contrastive learning method for 3D EM data, and use it to extract features of synapses from mouse visual cortex. SynapseCLR feature representations separate synapses by appearance and functionally important structural annotations. We demonstrate SynapseCLR's utility for valuable downstream tasks, including one-shot identification of defective synapse segmentations, dataset-wide similarity-based querying, and accurate imputation of annotations for unlabeled synapses, using manual annotation of only 0.2% of the dataset's synapses. In particular, excitatory versus inhibitory neuronal types can be assigned with >99.8% accuracy to individual synapses and highly truncated neurites, enabling neurite-enhanced connectomics analysis. Finally, we present a data-driven, unsupervised study of synaptic structural variation on the representation manifold, revealing its intrinsic axes of variation and showing that representations contain inhibitory subtype information.