Table 2.
Electrophysiological approaches adapted to functionally characterize brain organoids: The state-of-art.
| Methods | Scope | Application and results | Reference | |
|---|---|---|---|---|
| Individual cells | Current/Voltage clamp | Membrane potential and neuronal firing. Mechanistic information on ion channels. | Changes in resting membrane potentials. Cell maturation. Emergent active network (Single spikes, Burst events). Excitatory postsynaptic currents (EPSCs) Dopaminergic (mDA) neurons functionally mature. Neural development and diseases investigation. Improved long-term neuronal survival. | Hartfield et al., 2014; Paşca et al., 2015; Li et al., 2017; Di Lullo and Kriegstein, 2017; Giandomenico et al., 2018 |
| Optogenetics | Excitation or inhibition of the neuronal activity at high temporal and spatial resolution. Cellular polarization through light activation of specific DNA-encoded light-sensitive ion channels (i.e., optogenes) or inhibitory pumps. Cell therapy. | Modulation in real time of electrophysiological and neurochemical properties of mesencephalic dopaminergic (mesDA) neurons. Cell-type specificity, Optogene expression triggered. Broad diversity of cellular responses. | Steinbeck et al., 2015; Rajasethupathy et al., 2016; Klapper et al., 2017; Quadrato et al., 2017 | |
| Small cellular aggregations | Calcium imaging | Characterization of the Ca2+ status and changes in fluorescence induced by the binding of the Ca2+ ions with genetically encoded calcium indicators or small molecules based on the aminopolyearbowlie acid BAPTA | Homogeneous fluorescence induced by calcium detection reagents such as Fluo-4 direct. Emergence of spontaneous and single cell tracings of calcium induced by glutamate and TTX application. | Lancaster et al., 2013 |
| Network scale | Micro-electrode array (MEA) | Characterization of the extracellular electrophysiology. Acquisition of long-term spontaneous recordings and evoked responses induced by chemical or electrical stimulation at 60 or 120 up to 4,000 or 10,000 electrodes | Mono- and biphasic spikes closely in time. Firing frequency reduction induced by chemical perturbation (quinpirole treatment) on midbrain dopaminergic neurons (mDNs) Neuronal dynamics from spontaneous activity. | Monzel et al., 2017; Giandomenico et al., 2018 |