A proper excitatory/inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures
Authors: Eleonora Crocco, Ludovico Iannello, Fabrizio Tonelli, Gabriele Lagani, Luca Pandolfini, Marcello Ferro, Giuseppe Amato, Angelo Di Garbo e Federico Cremisi
Journal: Stem Cell Reports
DOI: 10.1016/j.stemcr.2025.102646
Introduction:
Mouse embryonic stem cells (mESCs) or human induced pluripotent cells (hiPSCs) are key tools for modeling the development of distinct encephalic regions in vitro by controlling different signaling pathways in precise time windows (Chambers et al., 2009; Chiaradia and Lancaster, 2020). Forebrain identity is acquired by default and retained primarily through BMP and Wnt inhibition (Bertacchi et al., 2015; Watanabe et al., 2005). Dorsal telencephalic (DT) progenitors are generated in vitro using the sonic Hedgehog (Shh) inhibitor, cyclopamine (Gaspard et al., 2008), while ventral telencephalic (VT) progenitors require Shh activation by the Shh agonist, SAG (Cederquist et al., 2019; Li et al., 2009). In vivo, the mature cerebral cortex forms after VT cells migrate, mainly from the medial ganglionic eminence (MGE) (Wonders and Anderson, 2006). These cells differentiate into GABAergic inhibitory interneurons that connect with glutamatergic excitatory neurons generated by local DT progenitors, establishing a balanced Excitatory/Inhibitory(E/I) ratio (Gelman and Marín, 2010; Lodato et al., 2011). Notably, an unbalanced E/I ratio is linked to brain disorders such as schizophrenia or autism spectrum disorders (Nelson and Valakh, 2015; Sohal and Rubenstein, 2019).
Keywords: spontaneous activity, excitatory/inhibitory balance, cortical development neuronal network activity, HD-MEAs, parvalbumin -positive neurons, functional connectivity, PV
