The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers that appear to be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.

哺乳动物大脑的成熟发生在出生后，神经元发育的这一阶段经常在神经系统疾病中受损，例如自闭症和精神分裂症。然而，调节出生后大脑成熟的机制尚不明确。通过纯化小鼠大脑发育中的神经元亚群，我们确定了在成熟哺乳动物大脑中运作的转录调节回路中的出生后转换。我们表明这种发育转变包括数百个细胞类型特异性神经元增强子的形成，这些神经元增强子似乎受神经元活动的调节。一旦被选中，这些增强子在整个成年期都很活跃，这表明它们在生命早期的形成塑造了神经元身份并调节了成熟的大脑功能。