EM connectomics reveals axonal target variation in a sequence-generating network

For us to interact with the world around us, our brains must plan and execute our movements and behaviors. For instance, although speaking is often quite effortless, it is also remarkably complex; all of the muscles in our vocal cords have to be activated at just the right moments to create words. It remains poorly understood how exactly the brain generates such precise timing signals that enable these movements. A specific portion of the songbird brain allows the bird to sing its song, a process that has clear parallels with human speech. Previous work had demonstrated that this region in the bird’s brain acts as a ‘clock’ for singing behavior, with individual brain cells active at just a single moment, or ‘tick’. Little consensus had been reached concerning how this might be achieved. Kornfeld, Benezra et al. have now used new anatomical methods to better understand how the songbird clock works. A technique called 3D electron microscopy allowed the connections between the neurons in the clock brain region to be seen directly. This revealed that these neurons form direct connections with each other, which is consistent with the idea that one ‘tick’ can lead to the next and so on, like a series of falling dominoes. Several mysteries remain to be resolved by future research. First, the connections that Kornfeld, Benezra et al. found are between cells that are quite distant from each other. This arrangement is fundamentally different from many other brain areas where neighboring cells are thought to work together. Second, although these key brain cells form appropriate connections to act as a clock, it is still not clear whether and how the network uses these connections during singing. By resolving these mysteries, we will establish a new framework for understanding how the brain encodes learned motor gestures that may help to spur innovative new approaches for combatting motor-related deficits due to injury or disease.