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SYNPRIME SIGNED

Presynaptic Regulatory Principles in Synaptic Plasticity, Neuronal Network Function, and Behaviour

Total Cost €

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EC-Contrib. €

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Partnership

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 SYNPRIME project word cloud

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

behaviours    12    cell    17    mediated    presynapses    vesicle    ours    synapse    refilled    plastic    vi    vitro    neuropsychiatric    mammalian    links    diseases    determinant    capss    pervasive    em    accessory    pool    synaptic    linked    intact    presynaptic    machinery    basic    lines    electrophysiological    delineation    exactly    memory    models    replacement    genetic    plasticity    biological    mechanisms    generate    fastest    psychiatry    functional    signalling    ki    membrane    stimulation    never    circuits    link    munc13s    examine    primed    proteins    strategies    release    thought    rates    cells    mouse    causal    sustain    tested    regulate    neuronal    dynamics    fusion    kis    science    event    brain    conditional    function    synapses    additional    hypothetical    functions    speed    ready    sv    lacking    circuit    behavioural    neural    newly    efficacy    kos    mainly    vivo    basis    optophysiological    ko    capacious    catholic    dependent    priming   

Project "SYNPRIME" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: MUENCHEN
postcode: 80539
website: n.a.

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 Germany [DE]
 Total cost 2˙495˙593 €
 EC max contribution 2˙495˙593 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) coordinator 2˙495˙593.00

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 Project objective

Neuronal signalling via synaptic vesicle (SV) fusion is the fastest membrane fusion event in mammalian cells. Its speed and the ability of presynapses to sustain SV fusion at high stimulation rates are key requirements for brain function. Plastic changes of SV fusion rates have long been thought to control complex brain processes such as working memory, but the link between presynaptic plasticity and complex brain functions remains hypothetical. A key determinant of presynaptic efficacy is that synapses maintain a release-ready or primed SV pool that can be refilled rapidly. SV priming is mediated by a set of dedicated priming proteins (Munc13s, CAPSs, and accessory proteins), which are of pervasive and essential functional importance for synaptic efficacy, and - based on in vitro studies - of capacious potential to regulate exactly the type of synaptic plasticity that is associated with brain circuit characteristics involved in complex behaviours. However, this 'catholic' role of the SV priming machinery in brain function has never been tested, mainly because essential genetic models for studies in vivo have been lacking. Using (i) 4 newly generated conditional KO and KI mouse lines, (ii) 17 additional KOs/KIs (12 ours), (iii) high-end EM approaches (iv) KO-replacement strategies, (v) electrophysiological and optophysiological analyses, and (vi) behavioural studies, we will examine the SV priming machinery in intact circuits in order to (a) define the mechanisms and cell biological basis of SV priming, of its dynamics, and of defined priming-dependent synaptic plasticity states, and to (b) define the causal links between SV priming, synapse function, synaptic plasticity, circuit characteristics, and behaviour. These studies will generate a comprehensive delineation of the role of SV priming in intact neural circuits, which is not only essential for basic science but also for psychiatry, because all key priming proteins are linked to neuropsychiatric diseases.

 Publications

year authors and title journal last update
List of publications.
2020 Lydia Maus, ChoongKu Lee, Bekir Altas, Sinem M. Sertel, Kirsten Weyand, Silvio O. Rizzoli, JeongSeop Rhee, Nils Brose, Cordelia Imig, Benjamin H. Cooper
Ultrastructural Correlates of Presynaptic Functional Heterogeneity in Hippocampal Synapses
published pages: 3632-3643.e8, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2020.02.083
Cell Reports 30/11 2020-04-15
2020 Dennis B. Nestvogel, Ricardo Martins Merino, Carolina Leon-Pinzon, Manuel Schottdorf, ChoongKu Lee, Cordelia Imig, Nils Brose, Jeong-Seop Rhee
The Synaptic Vesicle Priming Protein CAPS-1 Shapes the Adaptation of Sensory Evoked Responses in Mouse Visual Cortex
published pages: 3261-3269.e4, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2020.02.045
Cell Reports 30/10 2020-04-15
2018 Erwin Neher, Nils Brose
Dynamically Primed Synaptic Vesicle States: Key to Understand Synaptic Short-Term Plasticity
published pages: 1283-1291, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2018.11.024
Neuron 100/6 2020-04-15
2019 Francisco José López-Murcia, Kerstin Reim, Olaf Jahn, Holger Taschenberger, Nils Brose
Acute Complexin Knockout Abates Spontaneous and Evoked Transmitter Release
published pages: 2521-2530.e5, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.02.030
Cell Reports 26/10 2020-04-15
2017 Albrecht Sigler, Won Chan Oh, Cordelia Imig, Bekir Altas, Hiroshi Kawabe, Benjamin H. Cooper, Hyung-Bae Kwon, Jeong-Seop Rhee, Nils Brose
Formation and Maintenance of Functional Spines in the Absence of Presynaptic Glutamate Release
published pages: 304-311.e4, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2017.03.029
Neuron 94/2 2019-07-05
2016 Yuji Okamoto, Noa Lipstein, Yunfeng Hua, Kun-Han Lin, Nils Brose, Takeshi Sakaba, Mitsuharu Midorikawa
Distinct modes of endocytotic presynaptic membrane and protein uptake at the calyx of Held terminal of rats and mice
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.14643
eLife 5 2019-07-05
2017 Hiroshi Kawabe, Miso Mitkovski, Pascal S. Kaeser, Johannes Hirrlinger, Felipe Opazo, Dennis Nestvogel, Stefan Kalla, Anna Fejtova, Sophie E. Verrier, Simon R. Bungers, Benjamin H. Cooper, Frederique Varoqueaux, Yun Wang, Ralf B. Nehring, Eckart D. Gundelfinger, Christian Rosenmund, Silvio O. Rizzoli, Thomas C. Südhof, Jeong-Seop Rhee, Nils Brose
ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones
published pages: 1143-1161, ISSN: 0021-9525, DOI: 10.1083/jcb.201606086
The Journal of Cell Biology 216/4 2019-07-05
2017 Noa Lipstein, Nanda M. Verhoeven-Duif, Francesco E. Michelassi, Nathaniel Calloway, Peter M. van Hasselt, Katarzyna Pienkowska, Gijs van Haaften, Mieke M. van Haelst, Ron van Empelen, Inge Cuppen, Heleen C. van Teeseling, Annemieke M.V. Evelein, Jacob A. Vorstman, Sven Thoms, Olaf Jahn, Karen J. Duran, Glen R. Monroe, Timothy A. Ryan, Holger Taschenberger, Jeremy S. Dittman, Jeong-Seop Rhee, Gepke
Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder
published pages: 1005-1018, ISSN: 0021-9738, DOI: 10.1172/JCI90259
Journal of Clinical Investigation 127/3 2019-07-05

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