Simulating direct calcineurin suppression of protein kinase A in neurons
The NeuroSMS Partnering Project aims is to understand how signals from the second messengers calcium and cyclic AMP are integrated by the AKAP79 signalling complex that is essential for controlling synaptic strength.
The second messengers cAMP and calcium are key mediators of changes in the strength of synaptic connections. Such synaptic plasticity is considered a key component of memory formation including episodic memory in the hippocampus, and adaptive motor control and procedural memory in the basal ganglia. Interplay between calcium and cAMP signals is integral to normal changes in synaptic strength in response to specific patterns of activity. Signalling protein complexes orchestrate responses to second messengers. A signalling complex nucleated by the anchoring protein AKAP79 is essential for coordinating calcium and cAMP signals in the induction of long-term depression. This project has three related aims concerning the function of the AKAP79 signalling complex. The first aim is build kinetic models that incorporate signaling involving the enzymes protein kinase A and calcineurin that are both anchored to AKAP79. The second aim is to find parameters for the model using supercomputer-based fitting to data collected in our laboratory. The third aim is to run simulations to understand signalling dynamics within the complex that underlie different forms of synaptic plasticity.
Time Frame: 2021.07.01 – 2023.03.31
Origin: EBRAINS Research Infrastructure Voucher Programme 2020
Funding: HBP SGA3