biostudies-literatureColombi ITelethon FoundationTelethonEuropean Research CouncilJérôme Lejeune Foundation109438https://www.ebi.ac.uk/biostudies/studies/S-EPMC10966311biostudies-literatureUnknown27(4)Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population <i>average</i> level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a <i>mosaicism</i> of cells with either depolarizing or hyperpolarizing/inhibitory GABAergic responses exists in animals in health/disease at diverse developmental stages, including adulthood. Here, we showed that such mosaicism is present in wild-type (WT) and down syndrome (DS) neuronal networks, as assessed at increasing scales of complexity (cultures, brain slices, behaving mice). Nevertheless, WT mice presented a much lower percentage of cells with depolarizing GABA than DS mice. RiScienceHeterogeneous subpopulations of GABA_AR-responding neurons coexist across neuronal network scales and developmental stages in health and disease.PMC10966311TCP15021Cancedda LRastogi MChiappalone MColombi IChellali MMRosati SContestabile AParrini MAlberti MNanni MPotenzieri AfalseHeterogeneous subpopulations of GABA_AR-responding neurons coexist across neuronal network scales and developmental stages in health and disease.Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population <i>average</i> level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a <i>mosaicism</i> of cells with either depolarizing or hyperpolarizing/inhibitory GABAergic responses exists in animals in health/disease at diverse developmental stages, including adulthood. Here, we showed that such mosaicism is present in wild-type (WT) and down syndrome (DS) neuronal networks, as assessed at increasing scales of complexity (cultures, brain slices, behaving mice). Nevertheless, WT mice presented a much lower percentage of cells with depolarizing GABA than DS mice. R2024-01-01T00:00:00Z2024 Apr2026-07-16T00:19:10.874Z2025-05-31T23:11:52.724ZS-EPMC109663113854457410.1016/j.isci.2024.109438