A proper excitatory/inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures

Excitatory/inhibitory (E/I) balance is thought to play a key role in cortical activity development. We modeled an in vitro cortical network deployed of the inhibitory neurons normally migrating from the ventral telencephalon and implemented ventral telencephalic (VT) cultures and co-cultures with mixed proportions of dorsal telencephalic (DT) and VT neurons, containing distinct proportions of inhibitory neurons. Interestingly, these pure and mixed cultures developed different patterns of spontaneous activity and functional connectivity. Our findings highlighted a critical role for the inhibitory component in developing correlated network activity. Unexpectedly, networks with 7% of parvalbumin (PV)⁺ neurons were not able to generate appreciable network burst activity due to the development of a strong network inhibition, despite their lowest E/I ratio. Our observations support the notion that an optimal ratio of PV⁺ neurons during cortical development is essential for the establishment of local inhibitory networks capable of generating and spreading correlated activity.