The HUMANEUROMOD project, funded by the German Federal Ministry of Education and Research (BMBF) and carried out at the Justus‑Liebig University Giessen from 1 April 2020 to 30 June 2023, set out to create realistic, population‑based computer models of human cortical and hippocampal neurons. The goal was to investigate how epilepsy‑relevant ion‑channel mutations influence the excitability and resilience of hippocampal and neocortical cells in silico, and to provide models that can be freely shared with the scientific community.

Using the simulation environments NEURON, T2N, the TREES Toolbox and NetPyNE, the team developed new compartmental models of hippocampal CA1 pyramidal cells and granule cells. A new CA1 model was validated against freely available experimental data, compared with previously published models, and published in *Scientific Reports* (Tomko et al., 2021) and is available on ModelDB (ID 266901). Two further publications describe detailed simulations of GABA‑A‑channel mediated inhibition in CA1 pyramidal cells, co‑authored with Prof. Jedlicka and Prof. Werner Kilb from Mainz. These models, which capture chloride‑dependent GABAergic dynamics, are also shared on ModelDB (IDs 266811 and 266823).

In collaboration with Dr. Hermann Cuntz and Dr. Ruth Benavides‑Piccione, the project performed the first combined morphological and electrophysiological analysis of rodent and human CA1 pyramidal cells. The study revealed that human morphological reconstructions were incomplete and required repair by an “optimal wiring” algorithm. A software application for this repair process has been released online and will accompany a forthcoming publication (Groden et al., PLOS CB, 2024).

Population‑based modeling of ion‑channel expression was established for both hippocampal and cortical neurons. The resulting datasets, which capture the variability of channel densities across a large population of realistic morphologies, were published in *PLOS CB* (Schneider et al., 2023) and deposited on Zenodo (record 7863310). The models were used to simulate how morphological variability influences synaptically driven excitability across a broad set of neuron types drawn from the NeuroMorpho.Org database. This work uncovered a general principle linking dendritic architecture and synaptic input to neuronal excitability, reported in *Neuron* (Cuntz et al., 2021) and *eLife* (Castro et al., 2021). The findings provide a framework for predicting hypo‑ or hyper‑excitability in epilepsy and other neurological disorders.

Throughout the project, the team integrated human and animal data, performed extensive population‑based simulations, and validated all models against experimental recordings. The results were disseminated in 11 original research articles, two review papers, and three manuscripts are currently in preparation. The project’s open‑access policy ensured that all models, simulation scripts, and software tools are freely available to researchers worldwide, supporting 3R principles by reducing the need for new animal experiments. The collaborative effort involved experts in computational neuroscience, neuroanatomy, and epilepsy research, and exemplifies how interdisciplinary cooperation can advance our understanding of neuronal variability and disease mechanisms.