Researchers have mapped thousands of neural connections in the mouse brain using a new RNA barcoding technique, according to an April 7 announcement. The study was led by Boxuan Zhao, professor of cell and developmental biology at the University of Illinois Urbana-Champaign.
The new method allows scientists to better understand how neurons are connected, which is important for learning about brain function and diseases. Mapping these connections could help reveal how neurodegenerative diseases progress and potentially guide future treatments.
Zhao said, "When engineering a computer, you need to know the circuitry of the central processing unit. If you don't know how everything is wired together, you can't understand its function, optimize it or fix it when something breaks. We are approaching the brain the same way." He also said, "Our technology enables simultaneous mapping of thousands of neural connections with single-synapse resolution - a capability that doesn't exist in any current technology. It is directly applicable to understanding circuit dysfunction in neurodegenerative diseases and could provide a platform for developing circuit-guided therapeutic interventions."
The research team published their findings in Nature Methods. Their technique uses RNA "barcodes" attached to each neuron; specialized proteins carry these barcodes from the neuron's body to its synapses—the junctions where neurons connect. By sequencing these barcode pairs at synaptic junctions, researchers can determine which neurons are connected.
Zhao explained this process: "We translated the neural connectivity problem into a sequencing problem... If two balloons are tied together at the end, the two barcodes meet at the junction... We are doing this in the brain, just on the level of thousands of neuron cells." Using this approach called Connectome-seq, they mapped over 1,000 neurons in a specific mouse brain circuit and found previously unknown patterns between different cell types.
Looking ahead, Zhao said improvements already underway could eventually allow mapping of an entire mouse brain's connectivity. He added that Connectome-seq's speed and scale may accelerate research into neurological conditions by enabling comparison between healthy brains and those affected by disease: "With sequencing-based approaches... we could see where connections change... perhaps before symptoms even appear." Funding for this work came from grants provided by Wu Tsai Neurosciences Institute at Stanford University as well as other foundations.
