Figure 1.

Cell types/markers and functional properties reported in brain organoids in a time-dependent fashion, according to the literature. This timeline summarizes the emergence of the main mature cell types in brain organoids from distinct protocols, shown in months. Neurons start to appear in earlier times of culturing (~1 month). Dopaminergic and cholinergic neurons were found enriched in guided protocols. Markers of astrocytes and microglia increase from 1 month, while oligodendrocytes gradually emerge from 3 months of culturing. Early functional properties of developing brains such as giant depolarizing potentials (GDPs)-like can be recorded around 1 month of culture in guided protocols. Electrophysiological maturation such as synchronized burst firing activities, both action and spontaneous inhibitory/excitatory postsynaptic potentials, gradually emerge over time (from 2 months). More complex neural networks resulting from interconnectivity were reported by the presence of periodic oscillatory activity and synaptic plasticity and included long-term potentiation and depression (LTP and LTD) (~5–6 months). Neurons: Glu - glutamatergic; GABA, GABAergic; Dopa, dopaminergic; ACh, cholinergic.