Calcium Signals in Neurons During Early Development: Experiments and Theory

• Applicants: Privatdozent Dr. Friedrich Johenning; Professor Dr. Igor M. Sokolov, since 11/2019
• Subject Area: Developmental Neurobiology ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 327008147

Calcium is a key player in neuronal signaling, since it can serve both as electrical charge carrier at the membrane and biochemical second messenger. In this project we aim at its role in neuronal circuit formation during early postnatal brain development, which is characterized by the generation and elimination of dendrites, spines, and synapses. Neuronal plasticity and circuit formation have been shown to depend on cytoplasmic calcium elevations, which are necessary for dendritic and filopodial outgrowth as well as spine formation. We recently demonstrated that calcium release from intracellular stores via ryanodine receptors is able to generate signaling nanodomains involved in plasticity of dendritic spines (Johenning et al., PlosBiology, 2015).We propose to investigate the functional interaction between calcium signals and spine formation in an interdisciplinary experimental and theoretical approach. The dynamics of calcium is a phenomenon highly variable in space and time. Cytosolic calcium levels are modified by influx from the plasma membrane and the coordinated release from intracellular stores through receptor channels. Once calcium is released it diffuses into the cytosol and increases the open probability of neighboring intracellular calcium channels. This provides a self-amplifying mechanism, which is crucial for the generation of calcium waves.Using advanced experimental techniques we will characterize the distribution of calcium sources with a focus on intracellular stores in dendrites and the contributing factors for calcium signals. Theoretical research will then be based on the experimental results to propose and study a quantitative model of calcium waves in dendrites and spines. The theoretical methods, specifically adapted to the multi-scale nature of calcium concentration, allow a detailed investigation of the local distribution of calcium in micro- and nanodomains, which is not accessible by fluorescence microscopy. Our interdisciplinary approach will further identify the spatial patterning of calcium signals to the distribution of spines and branching pattern of dendrites. We aim at understanding how calcium signals govern the development of neonatal circuits.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Sten Rüdiger, until 11/2019