A proper excitatory/inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures
Eleonora Crocco1, Ludovico Iannello2, Fabrizio Tonelli1
1Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Pisa, Italy.
Stem Cell Reports
|September 26, 2025
Summary
Discover the critical role of inhibitory neurons in developing brain networks. An optimal ratio of parvalbumin (PV)+ neurons is essential for generating correlated cortical activity and establishing functional neural networks.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Computational Neuroscience
Background:
- Excitatory/inhibitory (E/I) balance is crucial for cortical development.
- Inhibitory neurons, originating from the ventral telencephalon, influence network activity.
- Understanding E/I balance is key to deciphering neural circuit formation.
Purpose of the Study:
- To investigate the role of inhibitory neuron proportions in developing cortical networks.
- To model in vitro cortical networks with varying E/I ratios.
- To determine the impact of specific inhibitory neuron subtypes on network activity patterns.
Main Methods:
- Cultured dorsal and ventral telencephalic neurons in pure and mixed configurations.
- Implemented in vitro cortical network models.
- Analyzed spontaneous network activity and functional connectivity.
Main Results:
- Pure and mixed neuronal cultures exhibited distinct activity patterns and connectivity.
- The inhibitory component critically influences the development of correlated network activity.
- Networks with 7% parvalbumin (PV)+ neurons showed suppressed burst activity due to strong inhibition, despite a low E/I ratio.
Conclusions:
- An optimal proportion of PV+ neurons is essential for establishing functional local inhibitory networks.
- Proper E/I balance, particularly concerning PV+ neuron density, is vital for generating and propagating correlated network activity during cortical development.


