Molecular mechanisms controlling synapse maintenance and plasticity

Neuronal circuits are formed through synaptic connections between defined populations of neurons. The regulated assembly and disassembly of synaptic connections ensures precise connectivity during development and during plasticity of the mature circuit. In contrast, the inappropriate loss of synaptic connections leads to a disruption of neuronal circuits and to progressive neurodegenerative disorders.

To identify the molecular and cellular pathways controlling synapse plasticity and maintenance we use the Drosophila neuromuscular junction (NMJ) as a model system. We performed a large-scale genetic screen of microtubule regulators and identified NudE, an auxiliary subunit of the Dynein motor complex, as essential for the control of axonal transport and synaptic stability. By combining genetic interactions and rescue assays with high resolution microscopy of individual synapses we identified a molecular sequence of events resulting in synapse disassembly with relevance to progressive motoneuron disease in humans. Furthermore, I will present data regarding a novel mTOR signaling pathway member essential for the control of functional and structural synaptic plasticity.

More on Prof. Dr. Jan Pielage