The human brain – all 86 billion neurons of it – is something of an enigma. Despite decades of research, our understanding of how it works remains limited, presenting a major roadblock in the quest to treat neurological disease and mental illness – one that the emerging field of connectomics, recently selected as Nature’s Method of the Year for 2025, seeks to dismantle. Connectomics strives to comprehensively map connections between synapses in an organism, in pursuit of a complete wiring diagram, or connectome, of interconnected neurons in the brain and nervous system. “Just as the genome is the set of all genes in an organism, the connectome is the set of all connections,” explained Paul Katz, Professor and Chair of Biology and Director of the Initiative on Neurosciences at the University of Massachusetts Amherst (MA, USA), speaking exclusively to BioTechniques. These maps can provide detailed insights into brain structure and function, furthering our grasp of behavior, cognition and memory. In short, they have the potential to transform neuroscience. Unfortunately, assembling a human connectome is easier said than done – current computational capacity is not up to the task of decoding our big brains – but researchers have made great strides in uncovering the intricate inner workings of the nervous systems of smaller, less complex species. How does connectomics work? Connectomics sits at the intersection of microscopy and AI, combining advanced imaging technologies, computational modeling and data analysis. Electron microscopy is integral to the approach, offering nanoscale resolution to allow the…