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Zebrafish bipolar

Timothy E McGinn, Diana M Mitchell, Peter C Meighan, Natalie Partington, Dylan C Leoni, Christina E Jenkins, Michael D Varnum, Deborah L Stenkamp
Adult zebrafish ( Danio rerio ) are capable of regenerating retinal neurons that have been lost due to mechanical, chemical, or light damage. In the case of chemical damage, there is evidence that visually mediated behaviors are restored after regeneration, consistent with recovery of retinal function. However, the extent to which regenerated retinal neurons attain appropriate morphologies and circuitry after such tissue-disrupting lesions has not been investigated. Adult zebrafish of both sexes were subjected to intravitreal injections of ouabain, which destroys the inner retina...
January 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Trevor J Hamilton, Adam Morrill, Kayla Lucas, Joshua Gallup, Megan Harris, Meghan Healey, Taylor Pitman, Melike Schalomon, Shannon Digweed, Martin Tresguerres
Scopolamine (hyoscine) is a muscarinic acetylcholine receptor antagonist that has traditionally been used to treat motion sickness in humans. However, studies investigating depressed and bipolar populations have found that scopolamine is also effective at reducing depression and anxiety symptoms. The potential anxiety-reducing (anxiolytic) effects of scopolamine could have great clinical implications for humans; however, rats and mice administered scopolamine showed increased anxiety in standard behavioural tests...
November 8, 2017: Scientific Reports
Bhavana Tiwari, Paula Kurtz, Amanda E Jones, Annika Wylie, James F Amatruda, Devi Prasad Boggupalli, Graydon B Gonsalvez, John M Abrams
Retrotransposons are a pervasive class of mobile elements present in the genomes of virtually all forms of life [1, 2]. In metazoans, these are preferentially active in the germline, which, in turn, mounts defenses that restrain their activity [3, 4]. Here we report that certain classes of retrotransposons ensure transgenerational inheritance by invading presumptive germ cells before they are formed. Using sensitized Drosophila and zebrafish models, we found that diverse classes of retrotransposons migrate to the germ plasm, a specialized region of the oocyte that prefigures germ cells and specifies the germline of descendants in the fertilized egg...
October 9, 2017: Current Biology: CB
Sheryll Corchuelo, Emanuel R M Martinez, Arno J Butzge, Lucas B Doretto, Juliana M B Ricci, Fernanda N Valentin, Laura S O Nakaghi, Gustavo M Somoza, Rafael H Nóbrega
Gonadotropin releasing hormone (GnRH) is one of the key players of brain-pituitary-gonad axis, exerting overall control over vertebrate reproduction. In zebrafish, two variants were characterized and named as Gnrh2 and Gnrh3. In this species, Gnrh3, the hypohysiotropic form, is expressed by neurons of the olfactory-retinal system, where it is related with food detection, intra/interspecific recognition, visual acuity and retinal processing modulation. Previous studies have reported the presence of Gnrh receptors in the zebrafish retina, but not yet in the zebrafish olfactory epithelium...
April 8, 2017: Molecular and Cellular Endocrinology
Peter Engerer, Sachihiro C Suzuki, Takeshi Yoshimatsu, Prisca Chapouton, Nancy Obeng, Benjamin Odermatt, Philip R Williams, Thomas Misgeld, Leanne Godinho
Conventionally, neuronal development is regarded to follow a stereotypic sequence of neurogenesis, migration, and differentiation. We demonstrate that this notion is not a general principle of neuronal development by documenting the timing of mitosis in relation to multiple differentiation events for bipolar cells (BCs) in the zebrafish retina using in vivo imaging. We found that BC progenitors undergo terminal neurogenic divisions while in markedly disparate stages of neuronal differentiation. Remarkably, the differentiation state of individual BC progenitors at mitosis is not arbitrary but matches the differentiation state of post-mitotic BCs in their surround...
May 2, 2017: EMBO Journal
Megan K Eldred, Mark Charlton-Perkins, Leila Muresan, William A Harris
To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight retinal organoids. Using a Spectrum of Fates zebrafish line, in which all different types of retinal neurons show distinct fluorescent spectra, we found that by 48 h in culture, the retinal organoids acquire a distinct spatial organisation, i.e. they became coarsely but clearly laminated...
March 15, 2017: Development
Katarzyna Misztal, Nikola Brozko, Andrzej Nagalski, Lukasz M Szewczyk, Marta Krolak, Katarzyna Brzozowska, Jacek Kuznicki, Marta B Wisniewska
The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus...
February 2017: Neuropharmacology
Rong-Wei Zhang, Xiao-Quan Li, Koichi Kawakami, Jiu-Lin Du
Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum...
2016: Nature Communications
Florence D D'Orazi, Xiao-Feng Zhao, Rachel O Wong, Takeshi Yoshimatsu
Stereotypic patterns of synaptic connections between neurons underlie the ability of the CNS to perform complex but circuit-specific information processing. Tremendous progress has been made toward advancing our understanding of how circuits are assembled during development, but whether the precision of this process can be recaptured after regeneration of neurons in the damaged CNS remains unclear. Here, we harnessed the endogenous regenerative capacity of the zebrafish retina to reconstruct the circuitry of neurons produced after damage...
September 12, 2016: Current Biology: CB
Paride Antinucci, Oniz Suleyman, Clinton Monfries, Robert Hindges
The orientation of visual stimuli is a salient feature of visual scenes. In vertebrates, the first neural processing steps generating orientation selectivity take place in the retina. Here, we dissect an orientation-selective circuit in the larval zebrafish retina and describe its underlying synaptic, cellular, and molecular mechanisms. We genetically identify a class of amacrine cells (ACs) with elongated dendritic arbors that show orientation tuning. Both selective optogenetic ablation of ACs marked by the cell-adhesion molecule Teneurin-3 (Tenm3) and pharmacological interference with their function demonstrate that these cells are critical components for orientation selectivity in retinal ganglion cells (RGCs) by being a source of tuned GABAergic inhibition...
July 25, 2016: Current Biology: CB
Lauren L Daniele, Farida Emran, Glenn P Lobo, Robert J Gaivin, Brian D Perkins
PURPOSE: Tail-anchored (TA) proteins contain a single hydrophobic domain at the C-terminus and are posttranslationally inserted into the ER membrane via the GET (guided entry of tail-anchored proteins) pathway. The role of the GET pathway in photoreceptors is unexplored. The goal of this study was to characterize the zebrafish pinball wizard mutant, which disrupts Wrb, a core component of the GET pathway. METHODS: Electroretinography, optokinetic response measurements (OKR), immunohistochemistry, and electron microscopy analyses were employed to assess ribbon synapse function, protein expression, and ultrastructure in 5-day-old zebrafish larvae...
June 1, 2016: Investigative Ophthalmology & Visual Science
Stella M K Glasauer, Robert Wäger, Matthias Gesemann, Stephan C F Neuhauss
Metabotropic glutamate receptors (mGluRs) are mainly known for regulating excitability of neurons. However, mGluR6 at the photoreceptor-ON bipolar cell synapse mediates sign inversion through glutamatergic inhibition. Although this is currently the only confirmed function of mGluR6, other functions have been suggested. Here we present Tg(mglur6b:EGFP)zh1, a new transgenic zebrafish line recapitulating endogenous expression of one of the two mglur6 paralogs in zebrafish. Investigating transgene as well as endogenous mglur6b expression within the zebrafish retina indicates that EGFP and mglur6b mRNA are not only expressed in bipolar cells, but also in a subset of ganglion and amacrine cells...
August 15, 2016: Journal of Comparative Neurology
Juliana M Rosa, Sabine Ruehle, Huayu Ding, Leon Lagnado
In daylight, the input to the retinal circuit is provided primarily by cone photoreceptors acting as band-pass filters, but the retinal output also contains neuronal populations transmitting sustained signals. Using in vivo imaging of genetically encoded calcium reporters, we investigated the circuits that generate these sustained channels within the inner retina of zebrafish. In OFF bipolar cells, sustained transmission was found to depend on crossover inhibition from the ON pathway through GABAergic amacrine cells...
April 20, 2016: Neuron
Stephan Maxeiner, Fujun Luo, Alison Tan, Frank Schmitz, Thomas C Südhof
Synaptic ribbons are large proteinaceous scaffolds at the active zone of ribbon synapses that are specialized for rapid sustained synaptic vesicles exocytosis. A single ribbon-specific protein is known, RIBEYE, suggesting that ribbons may be constructed from RIBEYE protein. RIBEYE knockdown in zebrafish, however, only reduced but did not eliminate ribbons, indicating a more ancillary role. Here, we show in mice that full deletion of RIBEYE abolishes all presynaptic ribbons in retina synapses. Using paired recordings in acute retina slices, we demonstrate that deletion of RIBEYE severely impaired fast and sustained neurotransmitter release at bipolar neuron/AII amacrine cell synapses and rendered spontaneous miniature release sensitive to the slow Ca(2+)-buffer EGTA, suggesting that synaptic ribbons mediate nano-domain coupling of Ca(2+) channels to synaptic vesicle exocytosis...
May 17, 2016: EMBO Journal
Yumi Ueki, Matthew S Wilken, Kristen E Cox, Laura Chipman, Nikolas Jorstad, Kristen Sternhagen, Milesa Simic, Kristy Ullom, Masato Nakafuku, Thomas A Reh
Müller glial cells are the source of retinal regeneration in fish and birds; although this process is efficient in fish, it is less so in birds and very limited in mammals. It has been proposed that factors necessary for providing neurogenic competence to Müller glia in fish and birds after retinal injury are not expressed in mammals. One such factor, the proneural transcription factor Ascl1, is necessary for retinal regeneration in fish but is not expressed after retinal damage in mice. We previously reported that forced expression of Ascl1 in vitro reprograms Müller glia to a neurogenic state...
November 3, 2015: Proceedings of the National Academy of Sciences of the United States of America
Renee W Chow, Alexandra D Almeida, Owen Randlett, Caren Norden, William A Harris
The mature vertebrate retina is a highly ordered neuronal network of cell bodies and synaptic neuropils arranged in distinct layers. Little, however, is known about the emergence of this spatial arrangement. Here, we investigate how the three main types of retinal inhibitory neuron (RIN)--horizontal cells (HCs), inner nuclear layer amacrine cells (iACs) and displaced amacrine cells (dACs)--reach their specific laminar positions during development. Using in vivo time-lapse imaging of zebrafish retinas, we show that RINs undergo distinct phases of migration...
August 1, 2015: Development
Ting Xu, Jing Zhao, Daqiang Yin, Qingshun Zhao, Bingzhi Dong
BACKGROUND: 2,2',4,4'-Tetrabromodiphenyl ether (BDE47) is a prevalent environmental pollutant and has been demonstrated to be a serious toxicant in both humans and animals, but little is known about the molecular mechanism underlying its toxic effect on the early development of vertebrates. BDE47-treated zebrafish larvae were found to present the light-related locomotion reduction in our previous study, therefore, we aimed to use high throughput sequencing to investigate the possible reasons from a transcriptomic perspective...
2015: BMC Genomics
Y Goldshmit, F Frisca, J Kaslin, A R Pinto, J-K K Y Tang, A Pébay, R Pinkas-Kramarski, P D Currie
Previously, we have demonstrated a role for fibroblast growth factor (Fgf) in spinal cord regeneration in both zebrafish and mouse. We have shown that exogenous Fgf2 treatment attenuates astrocytic gliosis and induces glia cells to become progenitors that undergo neurogenesis as well as differentiating into bipolar astrocytes that support axonal regeneration (Goldshmit et al., 2012, 2014). One of the downstream signaling target genes of Fgf is spry4, which acts as a feedback inhibitor for Fgf signaling. In this study we examined the effects of increased endogenous Fgf signaling, in spry4-/- mice, on the early events that occur after spinal cord injury (SCI)...
February 26, 2015: Neuroscience
Alaron A Lewis, Joseph T Mahoney, Neil Wilson, Susan E Brockerhoff
We previously identified Celsr3, an atypical cadherin, as essential for normal inhibitory circuit formation in the inner retina. Its absence during retinal development leads to increases in GABA receptor numbers on ON-bipolar cell terminals and consequent changes in retinal physiology, but does not cause obvious cell spacing or synaptic lamination defects. This study focuses on defining the subset of amacrine cells that express celsr3 during development of the wild type zebrafish retina. We have developed a BAC transgene expressing EGFP under the control of celsr3 promoter, Tg(celsr3:EGFP)...
January 2015: Experimental Eye Research
Bongsoo Suh, Stephen A Baccus
Sensory systems must be able to extract features of a stimulus to detect and represent properties of the world. Because sensory signals are constantly changing, a critical aspect of this transformation relates to the timing of signals and the ability to filter those signals to select dynamic properties, such as visual motion. At first assessment, one might think that the primary biophysical properties that construct a temporal filter would be dynamic mechanisms such as molecular concentration or membrane electrical properties...
October 2014: PLoS Biology
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