Fig. 1

Neurobiological mechanisms contributing to E/I balance. Schematic illustration of key mechanisms involved in establishing and regulating the balance between excitation and inhibition, highlighting the mechanisms and the ASD-related genes discussed in this review. In the cited reports, the iPSC technology has been exploited to develop human-based platforms in which to investigate the contribution of ASD-related genes to the different processes underlying E/I balance. a Establishment and maintenance of neuronal connectivity and E/I balance require all the salient features of neuronal morphology: the existence of branching dendrites and axons and the presence of neuronal synapses. Alterations in one or more of these features have been reported in several ASD models. b Excitatory and inhibitory neuron interplay results from the excitatory and inhibitory inputs converging on a neuron, as well as from the level of expression of postsynaptic glutamatergic (green) and GABAergic (red) receptors. c The application of technologies such as multi-electrode arrays and live calcium imaging has facilitated real-time, multi-point measurement of the activity of iPSC-derived neurons and allowed investigating developmental modifications of synaptic connectivity and network activity. d. Synaptic scaling is a form of homeostatic plasticity that operates to modify the global synaptic input (excitability) of a neuron in response to changes in circuit activity. One of the main mechanisms of synaptic scaling is the modification of the density and/or the size of synapses, and multiple electrophysiological techniques are used to analyze synaptic plasticity and neuronal excitability, including miniature excitatory/inhibitory postsynaptic currents