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Cai, D. J.

Publications and source records attributed to Cai, D. J..

21 records · Page 2Linked to original sources

Minian: An open-source miniscope analysis pipeline

Miniature microscopes have gained considerable traction for in vivo calcium imaging in freely behaving animals. However, extracting calcium signals from raw videos is a computationally complex problem and remains a bottleneck for many researchers utilizing single-photon in vivo calcium imaging. Despite the existence of many powerful analysis packages designed to detect and extract calcium dynamics, most have either key parameters that are hard-coded or insufficient step-by-step guidance and validations to help the users choose the best parameters. This makes it difficult to know whether the output is reliable and meets the assumptions necessary for proper analysis. Moreover, large memory demand is often a constraint for setting up these pipelines since it limits the choice of hardware to specialized computers. Given these difficulties, there is a need for a low memory demand, user-friendly tool offering interactive visualizations of how altering parameters at each step of the analysis affects data output. Our open-source analysis pipeline, Minian (Miniscope Analysis), facilitates the transparency and accessibility of single-photon calcium imaging analysis, permitting users with little computational experience to extract the location of cells and their corresponding calcium traces and deconvolved neural activities. Minian contains interactive visualization tools for every step of the analysis, as well as detailed documentation and tips on parameter exploration. Furthermore, Minian has relatively small memory demands and can be run on a laptop, making it available to labs that do not have access to specialized computational hardware. Minian has been validated to reliably and robustly extract calcium events across different brain regions and from different cell types. In practice, Minian provides an open-source calcium imaging analysis pipeline with user-friendly interactive visualizations to explore parameters and validate results.

neuroscience↗

ezTrack: An open-source video analysis pipeline for the investigation of animal behavior

Tracking small animal behavior by video is one of the most common tasks in the fields of neuroscience and psychology. Although commercial software exists for the execution of this task, commercial software often presents enormous cost to the researcher, and can also entail purchasing specific hardware setups that are not only expensive but lack adaptability. Moreover, the inaccessibility of the code underlying this software renders them inflexible. Alternatively, available open source options frequently require extensive model training and can be challenging for those inexperienced with programming. Here we present an open source and platform independent set of behavior analysis pipelines using interactive Python (iPython/Jupyter Notebook) that researchers with no prior programming experience can use. Two modules are described. One module can be used for the positional analysis of an individual animal across a session (i.e., location tracking), amenable to a wide range of behavioral tasks including conditioned place preference, water maze, light-dark box, open field, and elevated plus maze, to name but a few. A second module is described for the analysis of conditioned freezing behavior. For both modules, a range of interactive plots and visualizations are available to confirm that chosen parameters produce results that conform to the users approval. In addition, batch processing tools for the fast analysis of multiple videos is provided, and frame-by-frame output makes aligning the data with neural recording data simple. Lastly, options for cropping video frames to mitigate the influence of fiberoptic/electrophysiology cables, analyzing specified portions of time in a video, and defining regions of interest, can be implemented with ease.

neuroscience↗

Breakdown of spatial coding and neural synchronization in epilepsy

Temporal lobe epilepsy causes significant cognitive deficits in both human patients and rodent models, yet the specific circuit mechanisms that alter cognitive processes remain unknown. There is dramatic and selective interneuron death and axonal reorganization within the hippocampus of both humans and animal models, but the functional consequences of these changes on information processing at the neuronal population level have not been well characterized. To examine spatial representations of epileptic and control mice, we developed a novel wire-free miniature microscope to allow for unconstrained behavior during in vivo calcium imaging of neuronal activity. We found that epileptic mice running on a linear track had severely impaired spatial processing in CA1 within a single session, as place cells were less precise and less stable, and population coding was impaired. Long-term stability of place cells was also compromised as place cells in epileptic mice were highly unstable across short time intervals and completely remapped across a week. Because of the large-scale reorganization of inhibitory circuits in epilepsy, we hypothesized that degraded spatial representations were caused by dysfunctional inhibition. To test this hypothesis, we examined the temporal dynamics of hippocampal interneurons using silicon probes to simultaneously record from CA1 and dentate gyrus during head-fixed virtual navigation. We found that epileptic mice had a profound reduction in theta coherence between the dentate gyrus and CA1 regions and altered interneuron synchronization. In particular, dentate interneurons of epileptic mice had altered phase preferences to ongoing theta oscillations, which decorrelated inhibitory population firing between CA1 and dentate gyrus. To assess the specific contribution of desynchronization on spatial coding, we built a CA1 network model to simulate hippocampal desynchronization. Critically, we found that desynchronized inputs reduced the information content and stability of CA1 neurons, consistent with the experimental data. Together, these results demonstrate that temporally precise intra-hippocampal communication is critical for forming the spatial code and that desynchronized firing of hippocampal neuronal populations contributes to poor spatial processing in epileptic mice.

neuroscience↗