Recording, Analysis and Modeling of Mesoscale Neural Activities

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Introduction: Neural interactions in the brain are affected by transmission delays which may critically alter signal propagation across different brain regions in both normal and pathological conditions. The effect of interaction delays on the dynamics of the generic neural networks has been extensively studied by theoretical and computational models. However, the role of transmission delays in the development of pathological oscillatory dynamics in the basal ganglia (BG) in Parkinson's disease (PD) is overlooked.

Methods: Here, we investigate the effect of transmission delays on the discharge rate and oscillatory power of the BG networks in control (normal) and PD states by using a Wilson-Cowan (WC) mean-field firing rate model. We also explore how transmission delays affect the response of the BG to cortical stimuli in control and PD conditions.

Results: Our results show that the BG oscillatory response to cortical stimulation in control condition is robust against the changes in the inter-population delays and merely depends on the phase of stimulation with respect to cortical activity. In PD condition, however, transmission delays crucially contribute to the emergence of abnormal alpha (8–13 Hz) and beta band (13–30 Hz) oscillations, suggesting that delays play an important role in abnormal rhythmogenesis in the parkinsonian BG.

Discussion: Our findings indicate that in addition to the strength of connections within and between the BG nuclei, oscillatory dynamics of the parkinsonian BG may also be influenced by inter-population transmission delays. Moreover, phase-specificity of the BG response to cortical stimulation may provide further insight into the potential role of delays in the computational optimization of phase-specific brain stimulation therapies.

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The development of two-photon microscopy and Ca2+ indicators has enabled the recording of multiscale neuronal activities in vivo and thus advanced the understanding of brain functions. However, it is challenging to perform automatic, accurate, and generalized neuron segmentation when processing a large amount of imaging data. Here, we propose a novel deep-learning-based neural network, termed as NeuroSeg-II, to conduct automatic neuron segmentation for in vivo two-photon Ca2+ imaging data. This network architecture is based on Mask region-based convolutional neural network (R-CNN) but has enhancements of an attention mechanism and modified feature hierarchy modules. We added an attention mechanism module to focus the computation on neuron regions in imaging data. We also enhanced the feature hierarchy to extract feature information at diverse levels. To incorporate both spatial and temporal information in our data processing, we fused the images from average projection and correlation map extracting the temporal information of active neurons, and the integrated information was expressed as two-dimensional (2D) images. To achieve a generalized neuron segmentation, we conducted a hybrid learning strategy by training our model with imaging data from different labs, including multiscale data with different Ca2+ indicators. The results showed that our approach achieved promising segmentation performance across different imaging scales and Ca2+ indicators, even including the challenging data of large field-of-view mesoscopic images. By comparing state-of-the-art neuron segmentation methods for two-photon Ca2+ imaging data, we showed that our approach achieved the highest accuracy with a publicly available dataset. Thus, NeuroSeg-II enables good segmentation accuracy and a convenient training and testing process.

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Frontiers in Cellular Neuroscience

Memory processing in health and disease: linking behavioral, circuits, and molecular scales.
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