Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1 -/- mice.

Mutations of the GABA-A receptor subunit β1 () gene are found in autism patients. However, it remains unclear how mutations in may lead to autism. We generated mouse model, which showed autistic-like behaviors. We carried out RNA-seq on the hippocampus and found glutamatergic pathway may be involved. We further carried out single-cell RNA sequencing on the whole brain followed by qRT-PCR, immunofluorescence, electrophysiology, and metabolite detection on specific cell types. We identified the up-regulated in astrocytes, in neurons, glutamate, and the ratio of Glu/GABA in the hippocampus. Consistent with these results, increased NMDAR-currents and reduced GABAR-currents in the CA1 neurons were detected in mice. NMDAR antagonist memantine or inhibitor methionine sulfoximine could rescue the abnormal behaviors in mice. Our data reveal that upregulation of the glutamatergic synapse pathway, including NMDARs at neuronal synapses and glutamine exported by astrocytes, may lead to autistic-like behaviors.