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Nakai, N.

Publications and source records attributed to Nakai, N..

4 recordsLinked to original sources

End-to-end deep learning approach to mouse behavior classification from cortex-wide calcium imaging

Deep learning is a powerful tool for neural decoding, broadly applied to systems neuroscience and clinical studies. Interpretable and transparent models which can explain neural decoding for intended behaviors are crucial to identify essential features of deep learning decoders in brain activity. In this study, we examine the performance of deep learning to classify mouse behavioral states from mesoscopic cortex-wide calcium imaging data. Our convolutional neural network (CNN)-based end-to-end decoder combined with recurrent neural network (RNN) classifies the behavioral states with high accuracy and robustness to individual differences on temporal scales of sub-seconds. Using the CNN-RNN decoder, we identify that the forelimb and hindlimb areas in the somatosensory cortex significantly contribute to behavioral classification. Our findings imply that the end-to-end approach has the potential to be an interpretable deep learning method with unbiased visualization of critical brain regions. Author SummaryDeep learning is used in neuroscience, and it has become possible to classify and predict behavior from massive data of neural signals from animals, including humans. However, little is known about how deep learning discriminates the features of neural signals. In this study, we perform behavioral classification from calcium imaging data of the mouse cortex and investigate brain regions important for the classification. By the end-to-end approach, an unbiased method without data pre-processing, we clarify that information on the somatosensory areas in the cortex is important for distinguishing between resting and moving states in mice. This study will contribute to the development of interpretable deep-learning technology.

neuroscience↗

VR-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism

Functional connectivity (FC) can provide insight into cortical circuit dysfunction in neuropsychiatric disorders. However, dynamic changes in FC related to locomotion with sensory feedback remain unexplored. To investigate FC dynamics in locomoting mice, we developed mesoscopic Ca2+ imaging with a virtual reality (VR) environment. We find rapid reorganization of cortical FC in response to changing behavioral states. Using machine learning classification, behavioral states are accurately decoded. We then use our VR-based imaging system to study cortical FC in a mouse model of autism and find that locomotion states are associated with altered FC dynamics. Furthermore, we identify FC patterns involving the motor area as the most distinguishing features of the autism mice from wild-type mice during behavioral transitions, which might correlate with motor clumsiness in patients with autism. Our VR-based real-time imaging system provides invaluable information to understand FC dynamics linked to a behavioral abnormality of neuropsychiatric disorders.

neuroscience↗

Autism in a dish: ES cell models of autism with copy number variations reveal cell-type-specific vulnerability

Human genetics has identified numerous single nucleotide variations (SNVs) and copy number variations (CNVs) associated with autism spectrum disorders (ASD) and other psychiatric disorders. However, the lack of standardized biological resources impedes understanding of the common pathophysiology of ASD. Here, using next-generation chromosome engineering based on the CRISPR/Cas9 system, we established a biological resource including 65 genetically modified mouse embryonic stem cell (mESC) lines as genetic models of human SNVs and CNVs. To illustrate cell-type and CNV specific molecular features of ASD, we performed single-cell RNA sequencing (37,397 cells in total), morphological, and physiological analyses using 12 representative cell lines with CNVs highly associated with ASD. These results uncover gene ontology (GO) terms, canonical pathways, upstream regulators, and related neuropsychiatric disorders in a cell-type and CNV specific manner.

neuroscience↗

Encoding of social exploration by neural ensembles in the insular cortex

The insular cortex participates in diverse complex brain functions including sociality, yet little is known about their cellular bases. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely-moving and restrained social targets, we identified two subsets of AI neurons -a larger fraction of Social-ON cells and a smaller fraction of Social-OFF cells- that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which were preferentially active during exploration under particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons in encoding conjunctive information on social behavior and suggest that AI may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.

neuroscience↗