Elucidating neuronal circuits and their plasticity in the cerebral cortex is one of the important questions in neuroscience research. Here we report novel axonal trajectories and their plasticity in the mouse somatosensory barrel cortex. We selectively visualized layer 2/3 neurons using in utero electroporation and examined the axonal trajectories of layer 2/3 neurons. We found that the axons of layer 2/3 neurons preferentially run in the septal regions of layer 4 and named this axonal pattern "barrel nets." The intensity of green fluorescent protein in the septal regions was markedly higher compared with that in barrel hollows. Focal in utero electroporation revealed that the axons in barrel nets were indeed derived from layer 2/3 neurons in the barrel cortex. During development, barrel nets became visible at postnatal day 10, which was well after the initial appearance of barrels. When whisker follicles were cauterized within 3 d after birth, the whisker-related pattern of barrel nets was altered, suggesting that cauterization of whisker follicles results in developmental plasticity of barrel nets. Our results uncover the novel axonal trajectories of layer 2/3 neurons with whisker-related patterns and their developmental plasticity in the mouse somatosensory cortex. Barrel nets should be useful for investigating the pattern formation and axonal reorganization of intracortical neuronal circuits.

A central function of the brain is to plan, predict, and imagine the effect of movement in a dynamically changing environment. Here we show that in mice head-fixed in a plus-maze, floating on air, and trained to pick lanes based on visual stimuli, the asymmetric movement, and position of whiskers on the two sides of the face signals whether the animal is moving, turning, expecting reward, or licking. We show that (1) whisking asymmetry is coordinated with behavioral state, and that behavioral state can be decoded and predicted based on asymmetry, (2) even in the absence of tactile input, whisker positioning and asymmetry nevertheless relate to behavioral state, and (3) movement of the nose correlates with asymmetry, indicating that facial expression of the mouse is itself correlated with behavioral state. These results indicate that the movement of whiskers, a behavior that is not instructed or necessary in the task, can inform an observer about what a mouse is doing in the maze. Thus, the position of these mobile tactile sensors reflects a behavioral and movementpreparation state of the mouse.

Understanding the molecular mechanisms underlying the formation of selective intracortical circuitry is one of the important questions in neuroscience research. "Barrel nets" are recently identified intracortical axonal trajectories derived from layer 2/3 neurons in layer 4 of the primary somatosensory (barrel) cortex. Axons of layer 2/3 neurons are preferentially distributed in the septal regions of layer 4 of the barrel cortex, where they show whisker-related patterns. Because cadherins have been viewed as potential candidates that mediate the formation of selective neuronal circuits, here we examined the role of cadherins in the formation of barrel nets. We disrupted the function of cadherins by expressing dominant-negative cadherin (dn-cadherin) using in utero electroporation and found that barrel nets were severely disrupted. Confocal microscopic analysis revealed that expression of dn-cadherin reduced the density of axons in septal regions in layer 4 of the barrel cortex. We also found that cadherins were important for the formation, rather than the maintenance, of barrel nets. Our results uncover an important role of cadherins in the formation of local intracortical circuitry in the neocortex.

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