Orai mediated Calcium entry sets the excitability threshold of central dopaminergic neurons by regulation of gene expression DOI Open Access
Rishav Mitra, Shlesha Richhariya, Gaiti Hasan

et al.

Published: July 24, 2023

Maturation and fine-tuning of neural circuits frequently requires neuromodulatory signals that set the excitability threshold, neuronal connectivity synaptic strength. Here we present a mechanistic study how neuromodulator stimulated intracellular Ca 2+ signals, through store – operated channel Orai, regulate intrinsic properties by control developmental gene expression in flight promoting central dopaminergic neurons (fpDANs). The fpDANs receive cholinergic inputs for release dopamine at brain tripartite synapse sustains (Sharma Hasan, 2020). Cholinergic act on muscarinic acetylcholine receptor to stimulate endoplasmic reticulum (ER) localised inositol 1,4,5-trisphosphate followed ER-store depletion Orai mediated store-operated entry (SOCE). Analysis genetic, cellular molecular studies identified Orai-mediated as key regulator during circuit maturation. SOCE activates transcription factor Trithorax-like (Trl) which turn drives genes including Set2 , encodes histone 3 Lysine 36 methyltransferase (H3K36me3). function establishes positive feedback loop, essential receiving sustaining SOCE. Chromatin modifying activity changes epigenetic status ion signaling thus setting threshold determines maintenance long flight. Store-operated (SOCE) is required flight-promoting (fpDANs) late pupae early adults establish their profile.SOCE homeobox factor, ‘ ’ regulates modifiers E(z) generate balance between opposing signatures H3K36me3 H3K27me3 downstream genes.SOCE transcriptional loop ensure ( mAChR ) itpr) .The program functional maturation neurons, enabling transmission adult

Language: Английский

A global timing mechanism regulates cell-type-specific wiring programmes DOI
Saumya Jain, Ying Lin, Yerbol Z. Kurmangaliyev

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7899), P. 112 - 118

Published: Feb. 23, 2022

Language: Английский

Citations

41

Circuit mechanisms underlying embryonic retinal waves DOI Creative Commons
Christiane Voufo, Andy Quaen Chen, Benjamin E. Smith

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 15, 2023

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous comes in form retinal waves, comprised three stages persisting from embryonic day 16 (E16) to eye opening at postnatal 14 (P14). Though waves have been well characterized, little known about spatiotemporal properties or mechanisms mediating designated stage 1 waves. Using custom-built macroscope record calcium transients whole retinas, we show that are initiated several locations across retina and propagate broad range areas. Blocking gap junctions reduced frequency size nearly abolishing them. Global blockade nAChRs similarly abolished Thus, mediated by complex circuitry involving subtypes junctions. Stage mice lacking β2 subunit (β2-nAChR-KO) persisted with altered propagation were junction blocker. To assay impact on development, compared spatial distribution subtype ganglion cells, intrinsically photosensitive cells (ipRGCs), which undergo significant amount cell death, WT β2-nAChR-KO mice. We found developmental decrease ipRGC density preserved between mice, indicating processes regulating numbers distributions not influenced activity.

Language: Английский

Citations

18

Synaptic promiscuity in brain development DOI Creative Commons
Neele Wolterhoff, P. Robin Hiesinger

Current Biology, Journal Year: 2024, Volume and Issue: 34(3), P. R102 - R116

Published: Feb. 1, 2024

Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out their developmental context, readily form unspecific synapses. How does genome encode brain wiring in light this apparent contradiction? Synaptic specificity outcome long series processes and mechanisms before, during after synapse formation. much promiscuity permissible or necessary at moment partner choice depends on extent to which prior development restricts available partners subsequent corrects initially made can thereby play important roles precise connectivity, but also facilitate flexibility robustness. In review, we assess experimental evidence prevalence promiscuous formation development. Many well-established approaches are based genetic perturbation an assessment only adult; make it difficult pinpoint when given defect mechanism occurred. many cases, such studies reveal that restrict availability already Subsequently, choice, factors including competency, interaction dynamics molecular recognition further partners. The discussion through lens suggests algorithmic process neurons capable continuously prevented from making wrong choices, with no single time point sufficient explain outcome.

Language: Английский

Citations

8

SynBot is an open-source image analysis software for automated quantification of synapses DOI Creative Commons
Justin T Savage, J.J. Ramirez, W. Christopher Risher

et al.

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(9), P. 100861 - 100861

Published: Sept. 1, 2024

Language: Английский

Citations

8

Neuronal “parts list” and wiring diagram for a visual system DOI Creative Commons

Arie Matsliah,

Szi-chieh Yu, Krzysztof Kruk

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 13, 2023

A catalog of neuronal cell types has often been called a "parts list" the brain, and regarded as prerequisite for understanding brain function. In optic lobe

Language: Английский

Citations

17

Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis – A Drosophila Perspective DOI Creative Commons
Anjeli Mase,

Jordan Augsburger,

Katja Brückner

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 11, 2021

Across the animal kingdom, macrophages are known for their functions in innate immunity, but they also play key roles development and homeostasis. Recent insights from single cell profiling other approaches invertebrate model organism Drosophila melanogaster reveal substantial diversity among (plasmatocytes). Together with vertebrate studies that show genuine expression signatures of based on organ microenvironments, it is expected macrophage functional shaped by anatomical locations systemic conditions. In vivo evidence diverse has already been well established genetics: various aspects organogenesis, including embryogenesis nervous, digestive, reproductive systems. Macrophages further maintain homeostasis systems promote regeneration following damage injury. The interdependence interplay tissues local populations have implications understanding principles a wide range species.

Language: Английский

Citations

28

Temporal transitions in the postembryonic nervous system of the nematode Caenorhabditis elegans: Recent insights and open questions DOI Creative Commons
HaoSheng Sun, Oliver Hobert

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 142, P. 67 - 80

Published: June 7, 2022

After the generation, differentiation and integration into functional circuitry, post-mitotic neurons continue to change certain phenotypic properties throughout postnatal juvenile stages until an animal has reached a fully mature state in adulthood. We will discuss such changes context of nervous system nematode C. elegans, focusing on recent descriptions anatomical molecular that accompany postembryonic maturation neurons. summarize characterization genetic timer mechanisms control these temporal transitions or maturational changes, many but not all relate sexual animal. describe how temporal, spatial sex-determination pathways are intertwined sculpt emergence cell-type specific events. Finally, we lay out several unresolved questions should be addressed move field forward, both elegans vertebrates.

Language: Английский

Citations

20

Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior DOI Creative Commons
Sarah G. Leinwand, Kristin Scott

Neuron, Journal Year: 2021, Volume and Issue: 109(11), P. 1836 - 1847.e5

Published: April 28, 2021

Mature behaviors emerge from neural circuits sculpted by genetic programs and spontaneous evoked activity. However, how activity is refined to drive maturation of learned behavior remains poorly understood. Here, we explore transient hormonal signaling coordinates a state transition associative learning. We identify spontaneous, asynchronous in Drosophila learning memory brain region, the mushroom body. This declines significantly over first week adulthood. Moreover, this generated cell-autonomously via Cacophony voltage-gated calcium channels single cell type, α'/β' Kenyon cells. Juvenile hormone, crucial developmental regulator, acts transiently cells during young adult sensitive period downregulate enable subsequent enhanced Hormone animals therefore controls required for improved learning, providing insight into behavior.

Language: Английский

Citations

27

SynBot: An open-source image analysis software for automated quantification of synapses DOI Open Access
Justin T Savage, J.J. Ramirez, W. Christopher Risher

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 28, 2023

The formation of precise numbers neuronal connections, known as synapses, is crucial for brain function. Therefore, synaptogenesis mechanisms have been one the main focuses neuroscience. Immunohistochemistry a common tool visualizing synapses. Thus, quantifying synapses from light microscopy images enables screening impacts experimental manipulations on synapse development. Despite its utility, this approach paired with low throughput analysis methods that are challenging to learn and results variable between experimenters, especially when analyzing noisy tissue. We developed an open-source ImageJ-based software, SynBot, address these technical bottlenecks by automating analysis. SynBot incorporates advanced algorithms ilastik SynQuant accurate thresholding synaptic puncta identification, code can easily be modified users. use software will allow rapid reproducible phenotypes in healthy diseased nervous systems.

Language: Английский

Citations

11

Neuronal excitability as a regulator of circuit remodeling DOI Creative Commons
Oded Mayseless, Gal Shapira,

El Yazid Rachad

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(5), P. 981 - 989.e3

Published: Feb. 8, 2023

Postnatal remodeling of neuronal connectivity shapes mature nervous systems.1Luo L. O'Leary D.D.M. Axon retraction and degeneration in development disease.Annu. Rev. Neurosci. 2005; 28: 127-156https://doi.org/10.1146/annurev.neuro.28.061604.135632Crossref PubMed Scopus (664) Google Scholar,2Schuldiner O. Yaron A. Mechanisms developmental neurite pruning.Cell. Mol. Life Sci. 2014; 72: 101-119https://doi.org/10.1007/s00018-014-1729-6Crossref (118) Scholar,3Akin Zipursky S.L. Activity regulates brain the fly.Curr. Opin. Genet. Dev. 2020; 65: 8-13https://doi.org/10.1016/j.gde.2020.04.005Crossref (12) Scholar The pruning exuberant connections involves cell-autonomous non-cell-autonomous mechanisms, such as activity. Indeed, experience-dependent competition sculpts various excitatory circuits.4Johnson-Venkatesh E.M. Khan M.N. Murphy G.G. Sutton M.A. Umemori H. Excitability governs neural a hippocampal region specific manner.Development. 2015; 142: 3879-3891https://doi.org/10.1242/dev.121202Crossref (13) Scholar,5Katz L.C. Shatz C.J. Synaptic activity construction cortical circuits.Science. 1996; 274: 1133-1138https://doi.org/10.1126/science.274.5290.1133Crossref (2405) Scholar,6Hashimoto K. Ichikawa R. Kitamura Watanabe M. Kano Translocation "winner" climbing fiber to Purkinje cell dendrite subsequent elimination "losers" from soma developing cerebellum.Neuron. 2009; 63: 106-118https://doi.org/10.1016/j.neuron.2009.06.008Abstract Full Text PDF (141) Scholar,7Chung W.-S. Barres B.A. Selective remodeling: refining at neuromuscular junction.PLoS Biol. 7: e1000185https://doi.org/10.1371/JOURNAL.PBIO.1000185Crossref Scholar,8Walsh M.K. Lichtman J.W. In vivo time-lapse imaging synaptic takeover associated with naturally occurring synapse elimination.Neuron. 2003; 37: 67-73https://doi.org/10.1016/S0896-6273(02)01142-XAbstract (227) Scholar,9Tapia J.C. Wylie J.D. Kasthuri N. Hayworth K.J. Schalek Berger D.R. Guatimosim C. Seung H.S. Pervasive branch removal mammalian system birth.Neuron. 2012; 74: 816-829https://doi.org/10.1016/j.neuron.2012.04.017Abstract (89) Moreover, has been shown regulate growth cone motility stability neurites connections.10Cohan C.S. Kater S.B. Suppression elongation by electrical activity.Science. 1986; 232: 1638-1640https://doi.org/10.1126/SCIENCE.3715470Crossref Scholar,11O'Rourke N.A. Cline H.T. Fraser S.E. Rapid retinal arbors tectum without blockade transmission.Neuron. 1994; 12: 921-934https://doi.org/10.1016/0896-6273(94)90343-3Abstract (112) Scholar,12Lom B. Cohen-Cory S. Brain-derived neurotrophic factor differentially ganglion dendritic axonal arborization vivo.J. 1999; 19: 9928-9938https://doi.org/10.1523/JNEUROSCI.19-22-09928.1999Crossref Scholar,13Duch Mentel T. affects shape during steroid controlled Manduca sexta.J. 2004; 24: 9826-9837https://doi.org/10.1523/JNEUROSCI.3189-04.2004Crossref (29) Scholar,14Duch Stage-specific patterns affect motoneuron outgrowth metamorphosis sexta.Eur. J. 17: 945-962https://doi.org/10.1046/J.1460-9568.2003.02523.XCrossref However, whether inhibitory influences or how systems which is not clearly apparent fully understood. Here, we use Drosophila mushroom body (MB) model examine role axon γ-Kenyon cells. MB structure insects, implicated associative learning memory,15Heisenberg Borst Wagner Byers D. mutants are deficient olfactory learning.J. Neurogenet. 1985; 2: 1-30https://doi.org/10.3109/01677068509100140Crossref (558) Scholar,16Bilz F. Geurten B.R.H. Hancock C.E. Widmann Fiala Visualization distributed memory code brain.Neuron. 106: 963-976.e4https://doi.org/10.1016/J.NEURON.2020.03.010Abstract (0) receives mostly input antennal lobe.17Zheng Z. Lauritzen J.S. Perlman E. Robinson C.G. Nichols Milkie Torrens Price Fisher C.B. Sharifi et al.A complete electron microscopy volume adult melanogaster.Cell. 2018; 174: 730-743.e22https://doi.org/10.1016/j.cell.2018.06.019Abstract (410) Scholar,18Takemura S.Y. Aso Y. Hige Wong Lu Xu Rivlin P.K. Hess Zhao Parag connectome center brain.eLife. 2017; 6: e26975https://doi.org/10.7554/eLife.26975Crossref (217) circuit includes intrinsic neurons, called Kenyon cells (KCs), receive GABAergic anterior paired lateral (APL) neuron among other inputs. γ-KCs undergo stereotypic, steroid-hormone-dependent remodeling19Lee Luo Mosaic analysis repressible marker for studies gene function morphogenesis.Neuron. 22: 451-461https://doi.org/10.1016/s0896-6273(00)80701-1Abstract Scholar,20Lee Marticke Sung Robinow Cell-autonomous requirement USP/EcR-B ecdysone receptor Drosophila.Neuron. 2000; 807-818https://doi.org/10.1016/s0896-6273(00)00155-0Abstract that larval followed regrowth form connections.21Watts R.J. Hoopfer E.D. metamorphosis: evidence local ubiquitin-proteasome system.Neuron. 38: 871-885https://doi.org/10.1016/s0896-6273(03)00295-2Abstract We demonstrate silencing required γ-KC pruning. Furthermore, show this mechanistically achieved expression inward rectifying potassium channel 1 (irk1) combined inhibition APL likely via GABA-B-R1 signaling. These results support Hebbian-like rule "use it lose it," where can destabilize promote while excitability stabilizes existing connections.

Language: Английский

Citations

10