FOR 2419:  Plasticity versus Stability - Molecular Mechanisms of Synaptic Strength

• Subject Area: Medicine
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 278170285

The processing, storage and retrieval of information in the brain depend on neural circuits and the synapses which connect elements within the circuits. Although the gross structure of synaptic networks is stable for years, synaptic strength can change in the minute range in response to particular patterns of activity. The activity-dependent structural and functional changes that occur at synapses are known as synaptic plasticity and are thought to underlie learning and memory, forming the basis for cognitive function. How the balance between stability and flexibility is maintained is barely understood, especially as synaptic proteins turnover rapidly, in minutes to hours whereas memories may last decades. For instance, it is largely unknown how synaptic activation or silencing regulate the dynamic equilibrium of synaptic molecules or the long-term survival of dendritic spines. The list of cognitive and psychiatric disorders that are thought to be “synaptopathies” is growing and includes autism spectrum disorder and schizophrenia. The DFG Research Unit FOR 2419 applies anatomical, biochemical, physiological, genetic and optogenetic approaches to address the conflict between “plasticity” and “stability” at the synaptic level. The consortium combines expertise in molecular, cellular and systems neuroscience to ask how stable synaptic transmission is achieved, considering the constant turnover of synaptic constituents. Focusing on activity-dependent trafficking of mRNAs, proteins and organelles, FOR 2419 projects investigate molecular and cellular mechanisms that set synaptic lifetime and underlie memory. Our research focusses on highly topical questions at the core of human identity and provides a basis for understanding neuronal disease.

• DFG Programme: Research Units

Projects

• Coordination Funds (Applicant Kneussel, Ph.D., Matthias )
• Deciphering the functions of excitatory shaft synapses in pyramidal neurons (Applicant Mikhaylova, Marina )
• Mechanisms of Actomyosin-Dependent Regulation of Postsynaptic Function and Plasticity in Purkinje Cells (Applicant Wagner, Wolfgang )
• Structural and functional analysis of Cav1.2 mediated PM-ER contacts in the postsynaptic membrane (Applicants Grünewald, Kay ;  Heine, Martin )
• Structural Plasticity of Hippocampal Mossy Fiber Synapses (Applicant Kneussel, Ph.D., Matthias )
• Synaptic activity-dependent regulation of microtubule transport in the delivery of plasticity-related mRNAs and proteins (Applicant Kneussel, Ph.D., Matthias )
• Synaptic plasticity and stability in the context of hippocampal information processing (Applicant Wiegert, Jörn Simon )
• Synaptic plasticity: Impact on network stability and role of spine endoplasmic reticulum (Applicants Gee, Ph.D., Christine Elizabeth ;  Oertner, Thomas )
• The needs of a synapse - How local microsecretory systems and organelles serve synaptic function (Applicants Heisler, Frank Friedrich ;  Kreutz, Michael R. )
• The Role of TAO2 in Synapse Formation and Plasticity (Applicant Calderon de Anda, Froylan )

• Spokesperson: Professor Matthias Kneussel, Ph.D.