Mathematical generation of data-driven hippocampal CA1 pyramidal neurons and interneurons copies via A-GLIF models for large-scale networks covering the experimental variability range

Efficient and accurate large-scale networks are a fundamental tool in modeling brain areas, to advance our understanding of neuronal dynamics. However, their implementation faces two key issues: computational efficiency and heterogeneity. Computational efficiency is achieved using simplified neurons, whereas there are no practical solutions available to solve the problem of reproducing in a large-scale network the experimentally observed heterogeneity of the intrinsic properties of neurons. This is important, because the use of identical nodes in a network can generate artifacts which can hinder an adequate representation of the properties of a real network.

To this aim, we introduce a mathematical procedure to generate an arbitrary large number of copies of simplified hippocampal CA1 pyramidal neurons and interneurons models, which exhibit the full range of firing dynamics observed in these cells — including adapting, non-adapting and bursting. For this purpose, we rely on a recently published adaptive generalized leaky integrate-and-fire (A-GLIF) modeling approach, leveraging on its ability to reproduce the rich set of electrophysiological behaviors of these types of neurons under a variety of different stimulation currents.

The generation procedure is based on a perturbation of model’s parameters related to the initial data, firing block, and internal dynamics, and suitably validated against experimental data to ensure that the firing dynamics of any given cell copy remains within the experimental range. A classification procedure confirmed that the firing behavior of most of the pyramidal/interneuron copies was consistent with the experimental data. This approach allows to obtain heterogeneous copies with mathematically controlled firing properties. A full set of heterogeneous neurons composing the CA1 region of a rat hippocampus (approximately 1.2 million neurons), are provided in a database freely available in the live paper section of the EBRAINS platform.

By adapting the underlying A-GLIF framework, it will be possible to extend the numerical approach presented here to create, in a mathematically controlled manner, an arbitrarily large number of non-identical copies of cell populations with firing properties related to other brain areas.