Skibinski, G. et al. Nrf2 mitigates LRRK2- and α-synuclein–induced neurodegeneration by modulating proteostasis. Proc. Natl Acad. Sci. USA 114, 1165–1170 (2016).
Google Scholar
Skibinski, G., Nakamura, K., Cookson, M. R. & Finkbeiner, S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J. Neurosci. 34, 418–433 (2014).
Google Scholar
Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805–810 (2004).
Google Scholar
Miller, J. et al. Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat. Chem. Biol. 7, 925–934 (2011).
Google Scholar
Miller, J. et al. Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into huntington’s disease molecular pathogenesis. J. Neurosci. 30, 10541–10550 (2010).
Google Scholar
Tsvetkov, A. S. et al. Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration. Nat. Chem. Biol. 9, 586–592 (2013).
Google Scholar
Tsvetkov, A. S. et al. A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc. Natl Acad. Sci. USA 107, 16982–16987 (2010).
Google Scholar
Barmada, S. J. et al. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat. Chem. Biol. 10, 677–685 (2014).
Google Scholar
Barmada, S. J. et al. Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J. Neurosci. 30, 639–649 (2010).
Google Scholar
Surmeier, D. J., Obeso, J. A. & Halliday, G. M. Selective neuronal vulnerability in Parkinson disease. Nat. Rev. Neurosci. 18, 101–113 (2017).
Google Scholar
Rodrigue, K. M. et al. Risk factors for beta-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol. 70, 600–606 (2013).
Google Scholar
Linsley, J. W., Reisine, T. & Finkbeiner, S. Cell death assays for neurodegenerative disease drug discovery. Expert Opin. Drug Discov. 14, 901–913 (2019).
Kepp, O., Galluzzi, L., Lipinski, M., Yuan, J. & Kroemer, G. Cell death assays for drug discovery. Nat. Rev. Drug Discov. 10, 221–237 (2011).
Google Scholar
Arrasate, M. & Finkbeiner, S. Automated microscope system for determining factors that predict neuronal fate. Proc. Natl Acad. Sci. USA 102, 3840–3845 (2005).
Google Scholar
Finkbeiner, S., Frumkin, M. & Kassner, P. D. Cell-based screening: extracting meaning from complex data. Neuron 86, 160–174 (2015).
Google Scholar
Guo, F., Liu, X., Cai, H. & Le, W. Autophagy in neurodegenerative diseases: pathogenesis and therapy. Brain Pathol. 28, 3–13 (2018).
Google Scholar
Riss, T. L. et al. Cell Viability Assays. In Eli Lilly & Company and the National Center for Advancing Translational Sciences. (eds Markossian, S.) 317–342 (Assay Guidance Manual, Bethesda, MD, 2004).
van Ham, T. J., Mapes, J., Kokel, D. & Peterson, R. T. Live imaging of apoptotic cells in zebrafish. FASEB J. 24, 4336–4342 (2010).
Google Scholar
Zhang, J. et al. Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage. Nat. Commun. 4, 2157 (2013).
Google Scholar
Gorman, A. M. Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling. J. Cell. Mol. Med. 12, 2263–2280 (2008).
Google Scholar
Galluzzi, L. et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 25, 486–541 (2018).
Google Scholar
Tucker, B. & Lardelli, M. A rapid apoptosis assay measuring relative acridine orange fluorescence in zebrafish embryos. Zebrafish 4, 113–116 (2007).
Google Scholar
Horstick, E. J., Tabor, K. M., Jordan, D. C. & Burgess, H. A. Genetic ablation, sensitization, and isolation of neurons using nitroreductase and tetrodotoxin-insensitive channels. Methods Mol. Biol. 1451, 355–366 (2016).
Google Scholar
Abdelilah, S. et al. Mutations affecting neural survival in the zebrafish Danio rerio. Dev. 123, 217–227 (1996).
Google Scholar
Linsley, J. W. et al. Automated four-dimensional long term imaging enables single cell tracking within organotypic brain slices to study neurodevelopment and degeneration. Commun. Biol. 2, 155 (2019).
Google Scholar
Miyawaki, A. et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388, 882–887 (1997).
Google Scholar
Nagai, T., Sawano, A., Park, E. S. & Miyawaki, A. Circularly permuted green fluorescent proteins engineered to sense Ca2+. Proc. Natl Acad. Sci. USA 98, 3197–3202 (2001).
Google Scholar
Rose, T., Goltstein, P. M., Portugues, R. & Griesbeck, O. Putting a finishing touch on GECIs. Front. Mol. Neurosci. 7, 88 (2014).
Google Scholar
Lin, M. Z. & Schnitzer, M. J. Genetically encoded indicators of neuronal activity. Nat. Neurosci. 19, 1142–1153 (2016).
Google Scholar
Tominaga, K., Geusz, M. E., Michel, S. & Inouye, S. T. Calcium imaging in organotypic cultures of the rat suprachiasmatic nucleus. Neuroreport 5, 1901–1905 (1994).
Google Scholar
Ahrens, M. B., Huang, K. H., Narayan, S., Mensh, B. D. & Engert, F. Two-photon calcium imaging during fictive navigation in virtual environments. Front. Neural Circuits 7, 104 (2013).
Google Scholar
Huang K., et al. Predictive neural processing in adult zebrafish depends on shank3b. Preprint at bioRXiv. 2019.
Sheintuch, L. et al. Tracking the same neurons across multiple days in Ca(2+) imaging data. Cell Rep. 21, 1102–1115 (2017).
Google Scholar
Kim, D. H. et al. Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish. Nat. Methods 14, 1107–1114 (2017).
Google Scholar
Zhao, Y. et al. An expanded palette of genetically encoded Ca(2)(+) indicators. Science 333, 1888–1891 (2011).
Google Scholar
Suzuki, J. et al. Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA. Nat. Commun. 5, 4153 (2014).
Google Scholar
de Juan-Sanz, J. et al. Axonal endoplasmic reticulum Ca(2+) content controls release probability in CNS nerve terminals. Neuron 93, 867–881.e866 (2017).
Google Scholar
Skibinski, G. et al. Nrf2 mitigates LRRK2- and alpha-synuclein-induced neurodegeneration by modulating proteostasis. Proc. Natl Acad. Sci. USA 114, 1165–1170 (2017).
Google Scholar
Nakamura, K. et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J. Biol. Chem. 286, 20710–20726 (2011).
Google Scholar
Venderova, K. & Park, D. S. Programmed cell death in Parkinson’s disease. Cold Spring Harb. Perspect. Med. 2, a009365 (2012).
Merrilees, M. J., Beaumont, B. W. & Scott, L. J. Fluoroprobe quantification of viable and non-viable cells in human coronary and internal thoracic arteries sampled at autopsy. J. Vasc. Res. 32, 371–377 (1995).
Google Scholar
Crissman, H. A. & Steinkamp, J. A. Rapid, simultaneous measurement of DNA, protein, and cell volume in single cells from large mammalian cell populations. J. Cell Biol. 59, 766–771 (1973).
Google Scholar
Zhou, Y. & Danbolt, N. C. Glutamate as a neurotransmitter in the healthy brain. J. Neural Transm. 121, 799–817 (2014).
Google Scholar
Lewerenz, J. & Maher, P. Chronic glutamate toxicity in neurodegenerative diseases-What is the evidence? Front. Neurosci. 9, 469 (2015).
Google Scholar
Fujikawa, D. G. The role of excitotoxic programmed necrosis in acute brain injury. Comput. Struct. Biotechnol. J. 13, 212–221 (2015).
Google Scholar
Katayama, H., Kogure, T., Mizushima, N., Yoshimori, T. & Miyawaki, A. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem. Biol. 18, 1042–1052 (2011).
Google Scholar
Kimura, S., Noda, T. & Yoshimori, T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 3, 452–460 (2007).
Google Scholar
Huang, C. J. et al. Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes. J. Biol. Chem. 285, 339–348 (2010).
Google Scholar
Chi, H., Chang, H. Y. & Sang, T. K. Neuronal cell death mechanisms in major neurodegenerative diseases. Int. J. Mol. Sci. 19, 3082 (2018).
Barmada, S. J. et al. Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc. Natl Acad. Sci. USA 112, 7821–7826 (2015).
Google Scholar
Sawa, A., Tomoda, T. & Bae, B. I. Mechanisms of neuronal cell death in Huntington’s disease. Cytogenetic Genome Res. 100, 287–295 (2003).
Google Scholar
Morrice, J. R., Gregory-Evans, C. Y. & Shaw, C. A. Necroptosis in amyotrophic lateral sclerosis and other neurological disorders. Biochim. Biophys. Acta Mol. Basis Dis. 1863, 347–353 (2017).
Google Scholar
Kostrzewa, R. M. Review of apoptosis vs. necrosis of substantia nigra pars compacta in Parkinson’s disease. Neurotox. Res. 2, 239–250 (2000).
Google Scholar
Jager, K. J., van Dijk, P. C., Zoccali, C. & Dekker, F. W. The analysis of survival data: the Kaplan-Meier method. Kidney Int. 74, 560–565 (2008).
Google Scholar
Haston, K. M. & Finkbeiner, S. Clinical trials in a dish: the potential of pluripotent stem cells to develop therapies for neurodegenerative diseases. Annu. Rev. Pharm. Toxicol. 56, 489–510 (2016).
Google Scholar
Luigetti, M. et al. Heterozygous SOD1 D90A mutation presenting as slowly progressive predominant upper motor neuron amyotrophic lateral sclerosis. Neurol. Sci. 30, 517–520 (2009).
Google Scholar
Chen, H. et al. Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons. Cell Stem Cell 14, 796–809 (2014).
Google Scholar
Rose, T., Jaepel, J., Hubener, M. & Bonhoeffer, T. Cell-specific restoration of stimulus preference after monocular deprivation in the visual cortex. Science. 352, 1319–1322 (2016).
Google Scholar
Kim, C. K. et al. Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping. Front. Neural Circuits 8, 138 (2014).
Google Scholar
Martin-Jimenez, R., Campanella, M. & Russell, C. New zebrafish models of neurodegeneration. Curr. Neurol. Neurosci. Rep. 15, 33 (2015).
Google Scholar
Saleem, S. & Kannan, R. R. Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery. Cell Death Discov. 4, 45 (2018).
Xu, J., Wang, T., Wu, Y., Jin, W. & Wen, Z. Microglia colonization of developing zebrafish midbrain is promoted by apoptotic neuron and lysophosphatidylcholine. Dev. Cell 38, 214–222 (2016).
Google Scholar
Fett, M. E. et al. Parkin is protective against proteotoxic stress in a transgenic zebrafish model. PLoS ONE 5, e11783 (2010).
Google Scholar
Pyati, U. J., Look, A. T. & Hammerschmidt, M. Zebrafish as a powerful vertebrate model system for in vivo studies of cell death. Semin. Cancer Biol. 17, 154–165 (2007).
Google Scholar
Curado, S., Stainier, D. Y. & Anderson, R. M. Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies. Nat. Protoc. 3, 948–954 (2008).
Google Scholar
Zelenchuk, T. A. & Bruses, J. L. In vivo labeling of zebrafish motor neurons using an mnx1 enhancer and Gal4/UAS. Genes. 49, 546–554 (2011).
Google Scholar
Sternberg, J. R. et al. Optimization of a neurotoxin to investigate the contribution of excitatory interneurons to speed modulation in vivo. Curr. Biol. 26, 2319–2328 (2016).
Google Scholar
Tabor, K. M. et al. Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses. J. Neurophysiol. 112, 834–844 (2014).
Google Scholar
Muto, A. et al. Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish. Proc. Natl Acad. Sci. USA 108, 5425–5430 (2011).
Google Scholar
Attili, S. & Hughes, S. M. Anaesthetic tricaine acts preferentially on neural voltage-gated sodium channels and fails to block directly evoked muscle contraction. PLoS ONE 9, e103751 (2014).
Google Scholar
Lopez-Luna, J., Al-Jubouri, Q., Al-Nuaimy, W. & Sneddon, L. U. Impact of stress, fear and anxiety on the nociceptive responses of larval zebrafish. PLoS ONE 12, e0181010 (2017).
Google Scholar
Cheung, A. et al. A small-molecule inhibitor of skeletal muscle myosin II. Nat. Cell Biol. 4, 83–88 (2002).
Google Scholar
Zhou, W. et al. Non-sense mutations in the dihydropyridine receptor beta1 gene, CACNB1, paralyze zebrafish relaxed mutants. Cell Calcium 39, 227–236 (2006).
Google Scholar
Zahl, I. H., Samuelsen, O. & Kiessling, A. Anaesthesia of farmed fish: implications for welfare. Fish. Physiol. Biochem. 38, 201–218 (2012).
Google Scholar
Kanai, K. et al. Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 83, 734–738 (2012).
Google Scholar
Vossel, K. A. et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 70, 1158 (2013).
Google Scholar
Naumann, E. A., Kampff, A. R., Prober, D. A., Schier, A. F. & Engert, F. Monitoring neural activity with bioluminescence during natural behavior. Nat. Neurosci. 13, 513–520 (2010).
Google Scholar
Zhang, Y., Chen, X., Gueydan, C. & Han, J. Plasma membrane changes during programmed cell deaths. Cell Res. 28, 9–21 (2018).
Google Scholar
Chen, T. W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
Google Scholar
Reyes, R. C., Brennan, A. M., Shen, Y., Baldwin, Y. & Swanson, R. A. Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes. J. Neurosci. 32, 12973–12978 (2012).
Google Scholar
Minnella, A. M. et al. Excitotoxic superoxide production and neuronal death require both ionotropic and non-ionotropic NMDA receptor signaling. Sci. Rep. 8, 17522 (2018).
Google Scholar
Brennan-Minnella, A. M., Won, S. J. & Swanson, R. A. NADPH oxidase-2: linking glucose, acidosis, and excitotoxicity in stroke. Antioxid. Redox Signal. 22, 161–174 (2015).
Google Scholar
Brennan, A. M. et al. NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat. Neurosci. 12, 857–863 (2009).
Google Scholar
Berridge, M. J., Lipp, P. & Bootman, M. D. The versatility and universality of calcium signalling. Nat. Rev. Mol. cell Biol. 1, 11–21 (2000).
Google Scholar
Kanai, K. et al. Altered axonal excitability properties in amyotrophic lateral sclerosis: Impaired potassium channel function related to disease stage. Brain 129, 953–962 (2006).
Google Scholar
Poudel, G. R. et al. Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study. J. Psychiatry Neurosci. 39, 87–96 (2014).
Google Scholar
Jucker, M. & Walker, L. C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501, 45–51 (2013).
Google Scholar
Masnata, M. & Cicchetti, F. The evidence for the spread and seeding capacities of the mutant Huntingtin protein in in vitro systems and their therapeutic implications. Front. Neurosci. 11, 647 (2017).
Google Scholar
Jucker, M. & Walker, L. C. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann. Neurol. 70, 532–540 (2011).
Google Scholar
Abdelfattah, A. S. et al. A bright and fast red fluorescent protein voltage indicator that reports neuronal activity in organotypic brain slices. J. Neurosci. 36, 2458–2472 (2016).
Google Scholar
Pardo-Martin, C. et al. High-throughput in vivo vertebrate screening. Nat. Methods 7, 634–636 (2010).
Google Scholar
Saint-Amant, L. & Drapeau, P. Time course of the development of motor behaviors in the zebrafish embryo. J. Neurobiol. 37, 622–632 (1998).
Google Scholar
Kalueff, A. V. et al. Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond. Zebrafish 10, 70–86 (2013).
Google Scholar
Ghosh, S. & Hui, S. P. Regeneration of zebrafish CNS: adult neurogenesis. Neural Plast. 2016, 5815439 (2016).
Nicholson, C., ten Bruggencate, G., Stockle, H. & Steinberg, R. Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex. J. Neurophysiol. 41, 1026–1039 (1978).
Google Scholar
Egelman, D. M. & Montague, P. R. Calcium dynamics in the extracellular space of mammalian neural tissue. Biophys. J. 76, 1856–1867 (1999).
Google Scholar
Linsley, J. W. et al. Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3. Proc. Natl Acad. Sci. USA 114, E228–e236 (2017).
Google Scholar
Cen, H., Mao, F., Aronchik, I., Fuentes, R. J. & Firestone, G. L. DEVD-NucView488: a novel class of enzyme substrates for real-time detection of caspase-3 activity in live cells. FASEB J. 22, 2243–2252 (2008).
Google Scholar
Kwan, K. M. et al. The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Dev. Dyn. 236, 3088–3099 (2007).
Google Scholar
McGraw, H. F., Snelson, C. D., Prendergast, A., Suli, A. & Raible, D. W. Postembryonic neuronal addition in zebrafish dorsal root ganglia is regulated by Notch signaling. Neural Dev. 7, 23 (2012).
Google Scholar
Karlsson, J., von Hofsten, J. & Olsson, P. E. Generating transparent zebrafish: a refined method to improve detection of gene expression during embryonic development. Mar. Biotechnol. 3, 522–527 (2001).
Google Scholar
Daub, A., Sharma, P. & Finkbeiner, S. High-content screening of primary neurons: ready for prime time. Curr. Opin. Neurobiol. 19, 537–543 (2009).
Google Scholar
Afgan, E. et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Res. 44, W3–w10 (2016).
Google Scholar
Caster, A. H. & Kahn, R. A. Computational method for calculating fluorescence intensities within three-dimensional structures in cells. Cell. Logist. 2, 176–188 (2012).
Google Scholar
Li, Y. et al. A comprehensive library of familial human amyotrophic lateral sclerosis induced pluripotent stem cells. PLoS ONE 10, e0118266 (2015).
Google Scholar
Chambers, S. M. et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol. 27, 275–280 (2009).
Google Scholar
