| First Author | Colombi I | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 4 | Pages | 109438 |
| PubMed ID | 38544574 | Mgi Jnum | J:346702 |
| Mgi Id | MGI:7618013 | Doi | 10.1016/j.isci.2024.109438 |
| Citation | Colombi I, et al. (2024) Heterogeneous subpopulations of GABA(A)R-responding neurons coexist across neuronal network scales and developmental stages in health and disease. iScience 27(4):109438 |
| abstractText | Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population average level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a mosaicism 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. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behavior in DS mice. Moreover, we found heterogeneous GABAergic responses in developed control and trisomic human induced-pluripotent-stem-cells-derived neurons. Thus, a heterogeneous subpopulation of GABA-responding cells exists in physiological/pathological conditions in mouse and human neurons, possibly contributing to disease-associated behaviors. |
