Neurones and synapses for systemic models of psychiatric disorders.

We propose a mechanism-based modelling approach which brings together the most relevant features of neural dynamics and synaptic transmission for clinically valuable simulations of psychiatric disorders and their pharmaceutical treatment. It is based on a minimal, but physiologically justified concept, which allows to account for a great diversity of neuronal dynamics and synaptic mechanisms. It can simulate ionotropic as well as metabotropic receptors in addition to the effects of eventual co-transmitters and external neuromodulators. The proposed model can mimic the clinically most important aspects of synaptic disturbances, such as impaired transmitter availability or reduced number of postsynaptic receptors, for example due to their internalization as a function of transmitter concentration. It also allows evaluation of the effects of drugs with specific actions such as receptor agonists and antagonists or reuptake inhibitors. It is a major advantage of this physiologically based approach that it can be adjusted to different types of neurons and synapses, and also can be extended to more elaborate physiological situations, e. g. by including additional receptors or ion channels, whenever this is indicated by clinical or experimental data.

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