Unbiased discovery of neuronal architectures Science

Neuronal architectures comprise synaptically connected neurons distributed throughout the central nervous system, the coordinated activities of which orchestrate neurological functions ranging from breathing to movement and cognition. Disentangling these neuronal architectures and how they are disrupted in disease is a fundamental goal of neuroscience. Historically, this challenge has been addressed with a reductionist framework that translated hypotheses into the interrogation of discrete neuronal subpopulations based on a priori expectations. The advent of high-throughput methodologies, including whole–central nervous system imaging in rodent models and single-cell transcriptomic readouts, now enable the visualization and characterization of neuronal subpopulations throughout the central nervous system. Increases in scale further enable comparative experimental designs that can be navigated with computational frameworks. These advances augur a new era wherein neuronal architectures implicated in diverse neurological functions, yet obscured by the complexity of the central nervous system, can be exposed without bias and interrogated with genetically guided experimental manipulations.