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Berezhnoi, D.

Publications and source records attributed to Berezhnoi, D..

4 recordsLinked to original sources

SpikeCleaner: An Algorithm to Label Unit Quality After Automated Spike Sorting

GapAutomated spike sorting algorithms have revolutionized the way neuronal activity is extracted from extracellular recordings, yet they remain imperfect. Specifically, inaccurate acceptance of noise-based units not only leaves researchers with clusters that require extensive manual curation, an essential but time-consuming process, that also leads to significant subjectivity in the selection of units. In an era of high-density probes like Neuropixels, where an hour of data can exceed 80 GB, manual curation is no longer scalable, automation of standard criteria can speed data curation and ensure quality of datasets. Here, we developed a semi-automated curation pipeline to label the quality of units after automated curation by Kilosort. ApproachOur algorithm standardizes criteria for labeling of Noise, Multi-Unit Activity (MUA), and Good Units using a combination of spike rate, spike timing metrics (from autocorrelogram), and waveform-based physiological features such as peak amplitude, slopes, half-width, and inter-channel correlation. Based on these features, clusters are assigned standardized labels (good, noise, multi-unit activity) that can be imported directly into Phy, where they serve as curation aids rather than absolute classifications, supporting but not replacing expert judgment. Heuristically, "noise" units are those unlikely to be neuronal in origin; "MUA" includes units with significant neural contribution (i.e., neuronal waveform) but with some degree of clear imperfection to be further cleaned, and "good" units are those without any clear deviation from ideal unit criteria. By ensuring accurate selection of acceptable units, we enable robust downstream analyses such as neural decoding and longitudinal tracking of neuron identity. Thresholds for all metrics were chosen to maximize the matching of algorithm output to that of 2 expert manual curators. Of note, users may alter thresholds either based on their own judgment or using an included tool to semi-automatically find thresholds that optimize SpikeCleaner with their own expert curation. ResultsTo benchmark, we compared the outputs of our algorithm to expert-labels curated in Phy by two expert users across three recordings. SpikeCleaner achieved an average of 97% accuracy vs. experts & 92% F1 score in classifying Single Units. It achieved an accuracy of 97% & 92% F1 score in full-category agreement (SU, MUA, Noise), and 97% accuracy & 95% F1 score in distinguishing Neuronal vs. Non-Neuronal units.

neuroscience↗

Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism

There are substantial functional changes in the primary motor cortex (M1) in Parkinsons disease (PD). However, the temporal relationship between midbrain dopaminergic (DA) neurodegeneration, M1 circuit dysfunction, and Parkinsonian motor symptoms remains poorly understood. Using a genetic mouse model of progressive nigrostriatal DA degeneration ("MitoPark" mice), we determine the time course of M1 cellular dysfunction and skilled movement impairment as the midbrain DA neurons gradually degenerate. M1 pyramidal neuronal subtypes were identified using AAV-mediated retrograde labeling. During progressive DA loss, MitoPark mice developed gradually impaired performance in a reach-to-grasp single-food-pellet task. These impairments were detectable at a moderate motor stage of Parkinsonism. In vivo GCaMP6f imaging revealed that impaired skilled movement was associated with reduced cellular activity and movement responsiveness of M1 pyramidal neurons at a moderate motor stage of Parkinsonism. While both the corticospinal (CSp) and intratelencephalic (IT) neurons send glutamatergic inputs to the striatum, only the CSp neurons showed a selective and significant reduction in cellular activity and movement responsiveness during reaches. At the population level, we found that M1 pyramidal neurons include heterogeneous functional clusters with distinct temporal profiles in response to skilled movement. While movement encoding by different functional clusters is longitudinally stable in control mice, it degrades and diverges significantly in MitoPark mice. The impaired stability is further supported by a longitudinal analysis of individual neuronal activity related to movements. Together, these results provide novel insights into the emergence of M1 circuit pathophysiology at cellular and neural population levels during progressive Parkinsonism.

neuroscience↗

Sub-second characterization of locomotor activities of mouse models of Parkinsonism

The degeneration of midbrain dopamine (DA) neurons disrupts the neural control of natural behavior, such as walking, posture, and gait in Parkinsons disease. While some aspects of motor symptoms can be managed by dopamine replacement therapies, others respond poorly. Recent advancements in machine learning-based technologies offer opportunities to better understand the organizing principles of behavior modules at fine time scales and its dependence on dopaminergic modulation. In the present study, we applied the motion sequencing (MoSeq) platform to study the spontaneous locomotor activities of neurotoxin and genetic mouse models of Parkinsonism as the midbrain DA neurons progressively degenerate. We also evaluated the treatment efficacy of levodopa (L-DOPA) on behavioral modules at fine time scales. We revealed robust changes in the kinematics and usage of the behavioral modules that encode spontaneous locomotor activity. Further analysis demonstrates that fast behavioral modules with higher velocities were more vulnerable to loss of DA and preferentially affected at early stages of Parkinsonism. Last, L-DOPA effectively improved the velocity, but not the usage and transition probability, of behavioral modules in Parkinsonian animals. In conclusion, the hypokinetic phenotypes in Parkinsonism involve the decreased velocities of behavioral modules and their disrupted temporal organization during movement. Moreover, we showed that the therapeutic effect of L-DOPA is mainly mediated by its effect on the velocities of behavior modules at fine time scales. This work documents robust changes in the velocity, usage, and temporal organization of behavioral modules and their responsiveness to dopaminergic treatment under the Parkinsonian state. Significance StatementParkinsons disease is the second largest neurodegenerative disease without a cure. Detection of subtle Parkinsonian signs is critical for disease-modification by applying early interventions. The present work explores the possibility of using machine learning-based approaches for early detection of subtle behavioral changes in Parkinsonian animals and evaluating the therapeutic efficacy of dopaminergic medications.

neuroscience↗

Open-Source Platform for Kinematic Analysis of Mouse Forelimb Movement

We present an open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp task. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible. The protocol describes how to assemble the box, train mice to perform the task and process the video with the custom software pipeline to analyze forepaw kinematics. All the schematics, 3D models, code and assembly instructions are provided in the open GitHub repository. Graphical abstract

neuroscience↗