Table 1.

Overviewing comparison of rodent in vivo models

	Human relevance	Disease models	Systemic effects	Brain regions	Behaviour	Electrophysiology	Mechanistic studies	ADME/ TOX	HTS	Cost
Standard 2D cultures
Human primary	+++	++	–	++	–	++	++	+	+	++
Human iPSC	+++	+++	–	++	–	++	+++	+	+++	+++
Rodent primary	–	++	–	+++	–	+++	+++	+	+	++
Cell lines	+	+	–	–	–	+	+++	+	+++	++
Organoids
Human primary	+++	+++	–	++	–	–	++	–	–	++
Human iPSC	+++	+++	–	+	–	+	++	+	++	++
Rodent primary	–	+	–	+++	–	+	++	–	–	++
Cell lines	+	+	–	–	–	+	++	–	++	+
OoC
Human primary	+++	++	++	++	–	++	++	++	–	++
Human iPSC	+++	+++	++	++	–	++	+++	++	–	++
Rodent primary	–	++	++	+++	–	+++	+++	+	–	+
Cell lines	+	+	++	–	–	+	+++	++	–	+
Rodent in vivo	–	++	+++	+++	+++	++	+	++	–	+++

Table shows rodent in vivo models (the most commonly used mammal), standard 2D cell culture models, organoid cultures and OoC for their human specificity and their capacity to model human diseases, systemic effects, brain regionality, behaviour, drug absorption, distribution, metabolism and excretion, and toxicity (ADME/TOX). We also rate the possibility for electrophysiological studies, detailed mechanistic studies, high throughput studies (HTS), and the cost of the model. For the three in vitro models, we divided them into the accessible cell sources, human primary cells, rodent primary cell and hiPCS, and cell lines. Notably, we want to emphasize that human primary cells from the CNS are scarce. We further wish to highlight that this rating, the appropriateness of each model, varies for each specific study, and our rating should be used as a general guideline of what is possible to achieve with each model. – = poor/non-existent; + = OK; ++ = good; +++ = excellent.