Single cell methylation, RNA, and ATAC sequencing of brain tissue (amygdala) in inbred mouse strains

We carried out single-nucleus RNA, ATAC, and methylation sequencing of the whole mouse amygdala in two different strains to understand how genetic sequence variation affects molecular and epigenetic features in the mouse brain. In conjunction with sequencing data from the ventral hippocampus, we found that surprisingly, genetic effects from anywhere in the genome operate preferentially in excitatory neurons, consistent with a view that inhibitory neurons are gatekeepers of behavior, whose role in controlling the flow of information through excitatory neurons limits their tolerance to variation. This suggests that identifying genetic effects that disturb network function may be more fruitful for understanding complex behaviors and neuropsychiatric disease than looking for cell-type specific gene effects.