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SynChI SIGNED

Striatal cholinergic cell assemblies in movement disorders

Total Cost €

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EC-Contrib. €

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Partnership

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 SynChI project word cloud

Explore the words cloud of the SynChI project. It provides you a very rough idea of what is the project "SynChI" about.

combination    intracellular    brain    endoscopic    cues    chis    neurological    calcium    parkinson    record    recording    methodology    geci    origins    thereby    optogenetic    gcamp6    image    models    feasible    shown    share    orchestrate    relevance    synchronization    vitro    discharge    synchrony    microscopy    slices    hallmark    disease    di    neuronal    cutting    excessively    release    imaging    activation    employ    multiphoton    conjunction    vivo    moving    gaba    mice    signaling    striatal    chi    treat    dopamine    encoded    create    individual    mastered    transients    correct    normal    acute    induces    quantify    additionally    cholinergic    dimensional    synaptic    glutamate    presenting    elucidate    reveal    synchronous    hd    advent    classically    powerful    tools    deficits    huntington    afferents    datasets    simultaneously    therapeutic    larger    edge    exclusively    anesthetized    conditioned    genetically    pd    express    population    underscored    modern    mouse    structures    indicator    disorders    techniques    explore    pathological    interneurons   

Project "SynChI" data sheet

The following table provides information about the project.

Coordinator
THE HEBREW UNIVERSITY OF JERUSALEM 

Organization address
address: EDMOND J SAFRA CAMPUS GIVAT RAM
city: JERUSALEM
postcode: 91904
website: www.huji.ac.il

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE HEBREW UNIVERSITY OF JERUSALEM IL (JERUSALEM) coordinator 2˙000˙000.00

Map

 Project objective

Pathological neuronal synchrony is the hallmark of many neurological disorders, including Parkinson’s disease (PD) and Huntington’s disease (HD), which further share deficits in cholinergic signaling. Moreover, recent findings have underscored the therapeutic relevance of the synchrony among striatal cholinergic interneurons (ChI) that orchestrate this signaling. They have shown that excessively synchronous ChI discharge induces di-synaptic release of dopamine, GABA and glutamate. Here, I propose to elucidate how ChI synchronization is generated under normal and pathological conditions and thereby identify novel therapeutic targets to treat PD and HD. This study has only very recently become feasible with the advent of powerful tools that I have mastered to explore ChI synchrony. We will employ a combination of cutting-edge in vitro and in vivo techniques to simultaneously record a far larger population of pre-identified ChIs than is currently possible. We will express GCaMP6, a genetically encoded calcium indicator (GECI), exclusively in ChIs, and use multiphoton microscopy to image calcium transients from several ChIs simultaneously in conjunction with intracellular recording from individual ChIs in acute brain slices and in anesthetized mice. Additionally, we will use endoscopic GECI imaging in freely-moving classically conditioned mice. We will employ modern analyses that reveal low-dimensional structures in large neuronal datasets to quantify synchrony (1) during on-going activity; (2) during optogenetic activation of afferents; and (3), in the freely-moving mice, while presenting conditioned cues. Finally, we will study the origins of pathological synchrony in PD and HD mouse models and explore means to correct this condition. This comprehensive approach should explain the pathological ChI synchrony observed in PD; identify novel targets to treat PD and HD; and create a general methodology to study pathological synchrony in many other neurological disorders.

 Publications

year authors and title journal last update
List of publications.
2017 Jose de Jesus Aceves Buendia, Lior Tiroshi, Wei-Hua Chiu, Joshua A. Goldberg
Selective remodeling of glutamatergic transmission to striatal cholinergic interneurons after dopamine depletion
published pages: , ISSN: 0953-816X, DOI: 10.1111/ejn.13715
European Journal of Neuroscience 2020-01-21
2018 Joshua L. Plotkin, Joshua A. Goldberg
Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders
published pages: 107385841880788, ISSN: 1073-8584, DOI: 10.1177/1073858418807887
The Neuroscientist 2020-01-21
2016 Asami Tanimura, Sean Austin O. Lim, Jose de Jesus Aceves Buendia, Joshua A. Goldberg, D. James Surmeier
Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease
published pages: , ISSN: 1662-5137, DOI: 10.3389/fnsys.2016.00102
Frontiers in Systems Neuroscience 10 2020-01-21
2019 Lior Tiroshi, Joshua A. Goldberg
Population dynamics and entrainment of basal ganglia pacemakers are shaped by their dendritic arbors
published pages: e1006782, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006782
PLOS Computational Biology 15/2 2020-01-21
2019 Rotem Rehani, Yara Atamna, Lior Tiroshi, Wei-Hua Chiu, José de Jesús Aceves Buendía, Gabriela J. Martins, Gilad A. Jacobson, Joshua A. Goldberg
Activity Patterns in the Neuropil of Striatal Cholinergic Interneurons in Freely Moving Mice Represent Their Collective Spiking Dynamics
published pages: ENEURO.0351-18.2, ISSN: 2373-2822, DOI: 10.1523/eneuro.0351-18.2018
eneuro 6/1 2020-01-21

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