Neural circuit mechanisms that support the transformation of sensory inputs into number coding - Project Summary Number sense, the cognitive ability to represent and manipulate numbers, is found across various species, including mammals, birds, and insects, and is crucial for their survival. Among various species, number sense is particularly important for humans for their social and economic activities. People with numerical disorders, such as dyscalculia, which affects 3-5% of the population, face significant challenges in their lives. Despite the importance of number sense, the underlying neural circuit mechanisms remain poorly understood. Previous studies with monkeys have found neurons in the parietal and prefrontal cortical areas that selectively respond to specific numbers. These number coding neurons are the candidate neural substrates for numerical perception. However, the neural circuit mechanism that generates and maintains the number coding remains unknown. Understanding of the mechanism is crucial to understand the basis of numerical disorders and develop effective treatments. This research program investigates the neural circuit mechanisms that are responsible for the transformation of visual inputs into number coding in the brain. The vision-to-number transformation process involves multiple cortical areas spanning from sensory to association areas. To understand how sensory inputs are transformed into numbers across the cortical hierarchy, we developed novel head-fixed number discrimination behavior tasks for mice using virtual reality (VR). By combining the head-fixed VR tasks with a large field-of-view 2-photon calcium imaging and optogenetics, we will reveal how the brain transforms the extracted visual features into number coding and how the number selectivity is formed through inter-areal and local neural circuits. These animal experiments will be corroborated with network simulations using artificial intelligence (AI) trained to perform the same VR tasks. The results from this project will provide critical insights into the neural basis of number sense, an essential aspect of human intelligence, by revealing the transformation mechanism that bridges the gap between sensory and cognitive systems. Furthermore, our unique approach to combine large-scale in vivo imaging, optogenetics, AI-based network simulations, and novel virtual reality tasks that are compatible with training both mice and AI has the potential to become a powerful approach to understand neural mechanisms underlying cognitive functions that involve many brain areas in general. Therefore, the success of our project will have a broad impact on systems and cognitive neuroscience, and on the development of more effective treatment for number-related disorders.
