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A1 - Calcium dynamics in synapse-to-nucleus communication and network function

Principal investigator(s):

Universitšt Heidelberg
Im Neuenheimer Feld 364
69121 Heidelberg


Goethe Universitšt Frankfurt am Main
Goethe-Center for Scientific Computing (G-CSC)
Kettenhofweg 139
D-60325 Frankfurt am Main


Projects within the BCCN:

The aim of this project was to better understand the interplay between synaptic network activity, nuclear Ca2+ rises, gene regulation, and the consequences of their dysregulation during psychiatric disease and pathological aging. To these ends, we developed a model of intracellular Ca2+ signaling dynamics with a particular focus on signal transduction to the cell nucleus. The synapse-to-nucleus communication axis plays a central role in excitation-transcription coupling, which is an essential biochemical process in the consolidation of virtually all adaptive processes in the nervous system including memory, acquired neuroprotection, chronic pain, and drug addiction (Bas-Orth et al. 2016). Based on actual cellular geometries and experimental measurements, a realistic three-dimensional model of intracellular Ca2+ signaling dynamics with a particular focus on signal transduction to the cell nucleus was developed. This model incorporates both membrane potential-dependent ion channels and all appropriate Ca2+ sources and sinks (NMDA receptors, voltage-dependent Ca2+ channels, plasma membrane and endoplasmic reticular Ca2+ pumps, mobile and immobile cytoplasmic and nuclear Ca2+ buffers, and the ryanodine receptor and inositol triphosphate receptor intracellular Ca2+ release channels) (Mauceri et al. 2015). The starting density and distribution of all channels, pumps, and buffers, as well as enzyme activities (for the production and diffusion, for instance, of inositol triphosphate following synaptic activation) were determined based upon experimentally obtained parameters and reports available in the literature. We have also used our own Ca2+ imaging data to further refine the model (Mauceri et al. 2015). The model is suitable for studies of the calcium dynamics associated with synaptic activation and signal transduction, in particular of the characteristics of dendritic Ca2+ signal propagation and nuclear Ca2+ rises. The model may also be useful to model ageing and disease-related changes in synapse-to-nucleus communication caused by structural and/or functional alterations of neurons.

Participating groups:

Key publications:

Bas-Orth C, Tan YW, Oliveira AM, Bengtson CP, Bading H (2016) The calmodulin-binding transcription factor is required for long-term memory formation in mice. Learning & Memory 23, 313-321 (2016) .
Mauceri D, Hagenston AM, Schramm K, Weiss U, Bading H (2015) Nuclear calcium buffering capacity shapes neuronal architecture. J. Biol. Chem. 290, 23039-23049 .