Making flexible decisions in a dynamic environment is a powerful capacity of the mammalian brain. Despite decades of research at the behavioral and cognitive levels, the biological mechanisms implementing computations underlying flexible decision-making remain largely unknown. Here we developed an inferece-based flexible decision-making task in mice and combined in vivo two-photon imaging, large-scale neurophysiological recording and circuit manipulations to investigate the underlying neuronal mechanisms. Using cross-brain region circuit analysis, we show that the orbitofrontal-sensory cortical circuits implement an inference-based algorithm conferring a high degree of flexibility in rule-switching behavior. Using subcelullar two-photon imaging, we found that layer 5 cortical pyramidal neurons compartementalize different types of task information in dendritic and somatic subcellular domains, suggesting a dendritic integration mechanism for rule-based decisions. Using brain-wide electrophysiology, we further show that the representations for task variables of different degree of abstraction are orderly distributed across hierarchical brain regions. Our results provide new insights to the neuronal and circuit mechanisms implementing biological algorithms for flexible decision-making.


Dr Ning-long Xu is Senior Investigator and Lab Head at the Institute of Neuroscience/CEBSIT, Chinese Academy of Sciences. Dr Xu received his Ph.D. in 2006 from the Institute of Neuroscience, Chinese Academy of Sciences, with Dr. Mu-ming Poo, and subsequently conducted his postdoctoral research at Cold Spring Harbor Laboratory with Dr Zach Mainen and at HHMI Janelia Research Campus with Dr Jeff Magee. The laboratory of Dr Xu combines complex and highly controlled cognitive behavioral tasks in head-fixed mice and marmosets with high-resolution in vivo two-photon imaging and circuit analysis tools to investigate how neuronal circuits in mammalian brain implement computational algorithms that give rise to perception and cognition. Dr. Xu is the awardee of the National Natural Science Funds for Distinguished Young Scholars, and is leading several major national funding projects in China, including the decision-making project in the National Science and Technology Innovation 2030 Major Program.