Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex.

Autor:	Babij R; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10021, USA., Ferrer C; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Donatelle A; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Wacks S; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Buch AM; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Niemeyer JE; Department of Neurological Surgery, Weill Cornell Medicine, New-York Presbyterian Hospital, New York, NY 10021, USA., Ma H; Department of Neurological Surgery, Weill Cornell Medicine, New-York Presbyterian Hospital, New York, NY 10021, USA., Duan ZRS; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10021, USA., Fetcho RN; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10021, USA., Che A; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Otsuka T; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Schwartz TH; Department of Neurological Surgery, Weill Cornell Medicine, New-York Presbyterian Hospital, New York, NY 10021, USA., Huang BS; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., Liston C; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA., De Marco García NV; Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: nad2018@med.cornell.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2023 Jan 18; Vol. 111 (2), pp. 256-274.e10. Date of Electronic Publication: 2022 Nov 28.
DOI:	10.1016/j.neuron.2022.10.037
Abstrakt:	Dysfunction of gamma-aminobutyric acid (GABA)ergic circuits is strongly associated with neurodevelopmental disorders. However, it is unclear how genetic predispositions impact circuit assembly. Using in vivo two-photon and widefield calcium imaging in developing mice, we show that Gabrb3, a gene strongly associated with autism spectrum disorder (ASD) and Angelman syndrome (AS), is enriched in contralaterally projecting pyramidal neurons and is required for inhibitory function. We report that Gabrb3 ablation leads to a developmental decrease in GABAergic synapses, increased local network synchrony, and long-lasting enhancement in functional connectivity of contralateral-but not ipsilateral-pyramidal neuron subtypes. In addition, Gabrb3 deletion leads to increased cortical response to tactile stimulation at neonatal stages. Using human transcriptomics and neuroimaging datasets from ASD subjects, we show that the spatial distribution of GABRB3 expression correlates with atypical connectivity in these subjects. Our studies reveal a requirement for Gabrb3 during the emergence of interhemispheric circuits for sensory processing. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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