Simulation and validation of a mouse Purkinje cell multicompartmental model

Purkinje cells are part of the oldest and most complex neurons of the entire central nervous system. Their function is to integrate thousands of synaptic inputs coming from the cerebellar granular layer and the molecular layer interneurons. During the last six decades, many Purkinje cell models were built to explore their physiological properties. Only in 1994, the first multicompartmental model with HH ionic channels and a 3D reconstructed morphology was built. This model was rebuilt with new passive, active and axonal properties (Masoli et al., 2015).

The computational impact is very high, as each optimization requires at least 30 hours to complete 256 individuals and 7 generations. Therefore, this step is not included in the notebook.

The notebook contains a step-by-step description of each cell, starting with the visualization of the available results, to the actual analysis of the voltage/time traces and the definition of a set of parameters to validate the physiological results. The final step is to test each validated individual cell for the absence of the Axon Initial Segment (AIS) sodium channels. If a cell is still able to generate spontaneous firing, even without sodium channels, it is discarded as a non-physiological Purkinje cell. Only not-spiking models, without sodium channels in the AIS, are considered as correct.

The ionic channel mechanisms, passive properties and morphology were taken and adapted from a previously published guinea pig Purkinje cell model (Masoli et al,. 2015; Masoli and D’Angelo, 2017) ( and used for the automatic reconstruction and its validation.

(Code and testing - Stefano Masoli PhD)