Project

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Control of functional and structural plasticity of synapses by bone morphogenetic protein signaling

English title Control of functional and structural plasticity of synapses by bone morphogenetic protein signaling
Applicant Scheiffele Peter
Number 154455
Funding scheme Sinergia
Research institution Abteilung Zellbiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2015 - 31.12.2017
Approved amount 1'632'072.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Embryology, Developmental Biology
Genetics
Cellular Biology, Cytology

Keywords (8)

signaling; auditory system; Drosophila; knockout mice; plasticity; synapse formation; precerebellar system; trans-synaptic signaling

Lay Summary (German)

Lead
Kontrolle von funktioneller und struktureller synaptischer Plastizität durch Bone Morphogenic Signaling
Lay summary

Die Fähigkeit von Nervensystemen komplexe Informationen aufzunehmen, zu integrieren und spezifische Verhalten zu initiieren, basiert auf der präzisen Vernetzung von Neuronen. Lernprozesse werden durch spezifische Veränderungen in der Struktur und Funktion solcher neuronalen Netzwerke erreicht, eine Eigenschaft, die als Plastizität bezeichnet wird. Das Ziel dieses Projektes ist es die Mechanismen der neuronalen Plastizität besser zu verstehen. Die Arbeiten fokussieren dabei besonders auf molekulare Mechanismen, welche Veränderungen in der Aktivität individueller Neuronen in Veränderungen Ihrer Verbindungen umsetzen. Die beitragenden Gruppen bringen je einen wichtigen methodologischen Ansatz, um diese Fragestellung zu bearbeiten, von der Genetik in Fruchtfliegen und Mäusen zu zellbiologischen und elektrophysiologischen Studien.

Direct link to Lay Summary Last update: 04.02.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling
Vickers Evan, Osypenko Denys, Clark Christopher, Okur Zeynep, Scheiffele Peter, Schneggenburger Ralf (2020), LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling, in Scientific Reports, 10(1), 10047-10047.
Parvalbumin-Interneuron Output Synapses Show Spike-Timing-Dependent Plasticity that Contributes to Auditory Map Remodeling
Vickers Evan D., Clark Christopher, Osypenko Denys, Fratzl Alex, Kochubey Olexiy, Bettler Bernhard, Schneggenburger Ralf (2018), Parvalbumin-Interneuron Output Synapses Show Spike-Timing-Dependent Plasticity that Contributes to Auditory Map Remodeling, in Neuron, 1-16.
Local and long-range circuit elements for cerebellar function
Xiao Le, Scheiffele Peter (2018), Local and long-range circuit elements for cerebellar function, in Current Opinion in Neurobiology, 48, 146-152.
An organotypic slice culture to study the formation of calyx of Held synapses in-vitro
Kronander Elin, Michalski Nicolas, Lebrand Cécile, Hornung Jean-Pierre, Schneggenburger Ralf (2017), An organotypic slice culture to study the formation of calyx of Held synapses in-vitro, in PLOS ONE, 12(4), e0175964-e0175964.

Collaboration

Group / person Country
Types of collaboration
Wulfram Gerstner (EPFL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Jean-Marc Fritschy (Zurich) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
R. Coleman (University of Colorado) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
S. Sigrist (Freie Universität Berlin) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Matthijs Verhage (Amsterdam) Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Yishi Jin (UC San Diego) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Henry Markram (EPFL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
J. Javitch (Columbia University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
R. Baines (University of Manchester) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
S. Stowers (University of Montana) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Filipo Rijli (FMI, Basel) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Scott Small (Columbia University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
L. Pellizzoni (Columbia University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
A. Lazar (Columbia University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Tobias Boeckers (University of Ulm) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Anirvan Ghosh (Hoffmann La Roche) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration
P. Labrador (Trinity College Dublin) Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Thomas Su¨dhof (Stanford University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
T. Littleton (MIT) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
M. Nitabach (Yale University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Joung-Hun Kim (POSTECH) Korean Republic (South Korea) (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Thomas Bourgeron (Pasteur Institute) France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
M. Shirasu-Hiza (Columbia University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Henning Stahlberg (Biozentrum of the University of Basel) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Alain Che´dotal (Institute de la Vision, Paris) France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
156934 Role of Synaptotagmin isoforms in the Ca2+ - regulation of transmitter release at fast CNS synapses 01.10.2014 Project funding (Div. I-III)
127440 Transcriptional mechanisms of circuit formation and synapse specification 01.01.2010 Sinergia
176332 Afferent synaptic pathways in fear learning 01.10.2017 Project funding (Div. I-III)
157883 Request for a Serial Block Face Scanning Electron Microscope 01.12.2014 R'EQUIP

Abstract

The connectivity and plasticity of neuronal networks underlies movement and more complex behaviors in all animals, including humans. The overarching goal of this project is to understanding the interface between molecular mechanisms and experience-dependent plasticity that shape the specificity and function of synaptic connections in the nervous system. Many examples for functional and structural plasticity have been described in previous studies. However, there is a paucity of knowledge about the molecular and cell biological mechanisms that instruct such plasticity processes. A theme that recently emerged in molecular neuroscience is the “re-use” of neuronal patterning signals (that instruct early development) in later stages of neuronal development. Bone morphogenetic proteins (BMPs) represent one such example. Well-known for their roles in neural induction and patterning BMPs have novel, unexpected roles in synapse development. In this joint project, we will use a combination of genetic, cell biological, imaging, and electrophysiological approaches to test the hypothesis that BMP signaling controls structural and functional plasticity in the developing and mature nervous system. To this end, we will apply complementary expertise in the analysis of synaptic connectivity and function to address the following common goals: Common Goal 1: Probe cellular logic and directionality of synaptic BMP signalingThe first synaptic signaling function of BMPs identified was a retrograde, trans-synaptic signal at the Drosophila neuromuscular junction. However, for most systems and synapses the directionality and function of synaptic BMP signaling are unknown. Using genetic approaches to target specific neuronal cell populations we will dissect the directionality of BMP signaling in several neuronal systems. These efforts should enable us to identify fundamental principles of BMP signaling in synapse specification and synaptic plasticity.Common Goal 2: Identify molecular effectors of synaptic BMP signaling One primary read-out of BMP-signaling is the modification of transcriptional programs. Despite the central importance of such programs only a very small number of transcriptional targets for synaptic BMP signaling have been identified. We will employ a novel, cell type-specific chromatin-immunoprecipitation approach to identify novel transcriptional targets in pre- and postsynaptic cell populations. Function of such targets in synapse formation and synaptic plasticity will then be examined in loss-of-function studies. In addition to the canonical nuclear signaling functions of the BMP-pathway also local, non-canonical signaling mediators have been described. Using a combination of genetic manipulations and functional assays we will determine the relevance of such non-canonical signaling components for synapse formation and plasticity.Common Goal 3: Interplay of neuronal activity and BMP signaling in synaptic plasticity and learningAn emerging theme of recent studies is a coupling of neuronal activity and BMP signaling. We will jointly test such functions at the Drosophila neuromuscular junction, in the pontocerebellar projection system, and in cortical microcircuits. These studies will seek to identify BMP signaling nodes modified by neuronal activity. Finally, we will directly test the relevance of BMP-signaling for activity-dependent structural plasticity and the learning processes.
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