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bioRxiv · 10.1101/2025.02.28.640720

A proper Excitatory/Inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures

Crocco, E.·Iannello, L.·Tonelli, F.·Lagani, G.·Pandolfini, L.·Amato, G.·Di Garbo, A.·Cremisi, F.
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Abstract

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. HighlightsO_LIIn vitro neurogenesis models the development of mouse cortical network devoid of inhibitory neurons C_LIO_LICortical network with low inhibitory neuron ratio develops poor synchronized network activity C_LIO_LIGABA inhibition unmask intrinsic network ability to generate highly synchronized activity C_LIO_LINetwork response to single node stimulus depends on optimal inhibitory neuron ratio C_LIO_LIA proper excitatory/inhibitory ratio is necessary for the development of network burst activity C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/640720v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@3ee4org.highwire.dtl.DTLVardef@210461org.highwire.dtl.DTLVardef@1a693eforg.highwire.dtl.DTLVardef@13a6e4e_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Crocco, E., Iannello, L., Tonelli, F., Lagani, G., Pandolfini, L., Amato, G., Di Garbo, A., Cremisi, F.. 2025-03-01. A proper Excitatory/Inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures. https://doi.org/10.1101/2025.02.28.640720

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