Behavioral assays to study neural development in Xenopus laevis tadpoles

Khakhalin, Arseny S.; López, Javier; Aizenman, Carlos D.

doi:10.1101/2020.08.21.261669

Cited by 2 publications

(3 citation statements)

References 14 publications

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“…An overhead camera was used to acquire videos of the tadpoles, which were then tracked in EthoVision and processed offline in a custom MATLAB script (Khakhalin A, 2019; https://github.com/khakhalin/Xenopus-Behavior). Peak speed of each startle response was measured across a 2 s interval after stimulus delivery.…”

Section: Startle Habituation Responsementioning

confidence: 99%

Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

Gore

James

Huang

et al. 2021

eLife

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Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

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Section: Startle Habituation Responsementioning

confidence: 99%

Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

Gore

James

Huang

et al. 2021

eLife

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“…The Xenopus oocyte is a long‐favored model for electrophysiology studies of channel and other protein function (Kusano, Miledi, & Stinnakre, 1977; Limon, Reyes‐Ruiz, & Miledi, 2008; Miledi, Dueñas, Martinez‐Torres, Kawas, & Eusebi, 2004; Sigel & Minier, 2005; Ullah, Demuro, Parker, & Pearson, 2015; Vindas‐Smith et al, 2016), and electrophysiology tools have been adapted for use in embryos, tadpoles, and adults (Barkan, Zornik, & Kelley, 2017; Pratt & Khakhalin, 2013). Behavioral assays in tadpoles give a window into the outputs and functions of the nervous system (Khakhalin, 2020; Khakhalin, Lopez III, & Aizenman, 2020), during typical development and after genetic, pharmacological, or surgical perturbation. Many of these techniques have also been used to study adults at the molecular, cellular, tissue, and behavioral level (Barkan et al, 2017; Kelley et al, 2017; Pratt & Khakhalin, 2013).…”

Section: Beyond Fundamentals: Modeling Disorders Of the Brain In Xenopusmentioning

confidence: 99%

“…The morphogenetic movements and regulation of convergent extension have been studied extensively in Xenopus (Keller et al, 2000;Shindo, 2018), with several implications for our understanding of neural tube closure and associated congenital defects. Axon guidance (Erdogan, Ebbert, & Lowery, 2016;Koser et al, 2016;Slater, Hayrapetian, & Lowery, 2017;Thompson et al, 2019), synapse biology (Sakaki, Podgorski, Dellazizzo, Toth, & Haas, 2020), circuit function (Barkan et al, 2017;Kelley et al, 2017), and behavior (Khakhalin, 2020;Khakhalin et al, 2020) are all conveniently studied in frogs, and their evolutionary position affords them similar importance in answering questions about the evolution of these biological programs. Studies of the olfactory system and eye have shed light on how sensory organs develop and how they interface with different regions of the brain, in terms of both molecular interactions and connectivity (Liu, Hamodi, & Pratt, 2016).…”

Section: Outlook On Xenopus As a Model Of Brain Development And Diseasementioning

confidence: 99%

Xenopus leads the way: Frogs as a pioneering model to understand the human brain

Exner

Willsey

2020

Genesis

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Summary From its long history in the field of embryology to its recent advances in genetics, Xenopus has been an indispensable model for understanding the human brain. Foundational studies that gave us our first insights into major embryonic patterning events serve as a crucial backdrop for newer avenues of investigation into organogenesis and organ function. The vast array of tools available in Xenopus laevis and Xenopus tropicalis allows interrogation of developmental phenomena at all levels, from the molecular to the behavioral, and the application of CRISPR technology has enabled the investigation of human disorder risk genes in a higher‐throughput manner. As the only major tetrapod model in which all developmental stages are easily manipulated and observed, frogs provide the unique opportunity to study organ development from the earliest stages. All of these features make Xenopus a premier model for studying the development of the brain, a notoriously complex process that demands an understanding of all stages from fertilization to organogenesis and beyond. Importantly, core processes of brain development are conserved between Xenopus and human, underlining the advantages of this model. This review begins by summarizing discoveries made in amphibians that form the cornerstones of vertebrate neurodevelopmental biology and goes on to discuss recent advances that have catapulted our understanding of brain development in Xenopus and in relation to human development and disease. As we engage in a new era of patient‐driven gene discovery, Xenopus offers exceptional potential to uncover conserved biology underlying human brain disorders and move towards rational drug design.

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Behavioral assays to study neural development in Xenopus laevis tadpoles

Cited by 2 publications

References 14 publications

Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

Xenopus leads the way: Frogs as a pioneering model to understand the human brain

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