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Locomotion is fundamental to every animal’s existence. At the same time, motor deficits are common in many neurological and psychiatric diseases. Spinal cord activity underlies all locomotor output, while also being a source of sensory signals about the external world and state of the body. Our lab combines voltage-imaging, fictive behavior in a virtual environment, calcium-imaging and optogenetics to investigate the dynamics and timing of spinal circuits during locomotor behavior in the zebrafish. By investigating both the cellular and functional diversity of the entire intact spinal cord circuitry, our work will lead to a deeper understanding of what activity drives different behaviors, how neural networks generate dynamic but stable motor outputs, and which spinal cord activity is sent back to the brain. These insights are expected to have a broad relevance from fundamental neuroscience to motor deficits in neurology and psychiatry. |
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A. Experimental setup for parallel light sheet voltage imaging and virtual behavior. The larval zebrafish is paralyzed and presented with a visual stimulus from below. An extracellular electrode records fictive locomotion which in turn changes the stimulus. |
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| B. Example traces of parallel recorded membrane voltage using a genetically encoded voltage indicator. Traces are color coded according to whether the neuron is oscillating (red) or not (purple). The corresponding fictive locomotion (VNR) and speed of the visual feedback are shown below. |
Main publications:
Eom M, Han S, Park P, Kim G, Cho ES, Sim J, Lee KH, Kim S, Tian H, Böhm UL, Lowet E, Tseng HA, Choi J, Lucia SE, Ryu SH, Rózsa M, Chang S, Kim P, Han X, Piatkevich KD, Choi M, Kim CH, Cohen AE, Chang JB, Yoon YG. Statistically unbiased prediction enables accurate denoising of voltage imaging data. Nat Methods. 2023 Oct;20(10):1581-1592. doi: 10.1038/s41592-023-02005-8. Epub 2023 Sep 18. PubMed PMID: 37723246; PubMed Central PMCID: PMC10555843.
Böhm UL, Kimura Y, Kawashima T, Ahrens MB, Higashijima SI, Engert F, Cohen AE. Voltage imaging identifies spinal circuits that modulate locomotor adaptation in zebrafish. Neuron. 2022 Apr 6;110(7):1211-1222.e4. doi: 10.1016/j.neuron.2022.01.001. Epub 2022 Jan 31. PubMed PMID: 35104451; PubMed Central PMCID: PMC8989672.
Xie ME, Adam Y, Fan LZ, Böhm UL, Kinsella I, Zhou D, Rozsa M, Singh A, Svoboda K, Paninski L, Cohen AE. High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo. Cell Rep. 2021 Apr 6;35(1):108954. doi: 10.1016/j.celrep.2021.108954. PubMed PMID: 33826882; PubMed Central PMCID: PMC8095336.
Fan LZ, Kheifets S, Böhm UL, Wu H, Piatkevich KD, Xie ME, Parot V, Ha Y, Evans KE, Boyden ES, Takesian AE, Cohen AE. All-Optical Electrophysiology Reveals the Role of Lateral Inhibition in Sensory Processing in Cortical Layer 1. Cell. 2020 Feb 6;180(3):521-535.e18. doi: 10.1016/j.cell.2020.01.001. Epub 2020 Jan 23. PubMed PMID: 31978320; PubMed Central PMCID: PMC7259440.
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