What drives decision-making in the brain? Imagine a behavioral task during which a mouse in a maze learns that a cue means it should turn left to get a reward. After weeks of training to learn this, the cue shows up, and the mouse needs to decide to turn left or right. What makes the mouse turn left? During the task, neurons in a specific part of the cortex - called the posterior parietal cortex or PPC - become associated with left or right turns. These neurons are not only active during a turn but also before the mouse turns, so their activity can predict a turn direction. Are these neurons driving decisions? This age-old question is hard to answer with neuronal activity studies alone, and more knowledge was needed about how left- and right-turn neurons connect with each other. And that’s exactly what connectomics is about.
Connectomics is a research field that aims to make comprehensive wiring maps of brain circuits. To build those maps, researchers use electron microscopy (EM) to image thousands of very thin sections of the brain. In a new study published in Nature on February 21, Aaron Kuan, PhD, assistant professor of Neuroscience, and his collaborators used a custom-built automated EM system to image a decision-making circuit within the mouse brain. They needed months of uninterrupted (and automated) imaging time, and an even longer period to trace synapses and dendrites from each image, to finally reconstruct the circuit. By combining this circuit map, or connectome, with a behavioral decision-making task and real-time recording of neurons, the team discovered a pattern of circuit connections – a circuit motif – they called opponent inhibition: when an excitatory left-turn neuron is activated, it suppresses right-turn activity through inhibitory neurons.