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. However, the modeling of cortical networks with different E/I ratios is not feasible in vivo . To address this point, we modeled an in vitro cortical network deployed of the inhibitory neurons normally migrating from the ventral telencephalon. Moreover, we implemented striatal cultures and co-cultures with mixed proportions of cortical and striatal neurons. The resulting cultures contained various proportions of inhibitory Parvalbumin (PV) ⁺ neurons, ranging from 7% to 73%. Interestingly, these pure and mixed cortical/striatal cultures exhibited four distinct patterns of spontaneous activity and functional connectivity. Our findings highlighted a critical role for the inhibitory component in developing correlated network activity. Unexpectedly, cortical networks with 7% of 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.