The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

Abnormal development of GABAergic interneurons in the prefrontal cortex (PFC) is implicated in a number of psychiatric disorders. Yet, developmental mechanisms for these neurons are poorly understood. Here we show that the retinoic acid-degrading enzyme CYP26B1 is temporally expressed specifically in postnatal frontal cortex in mice, and its genetic deletion results in an increased density of parvalbumin (PV)-expressing interneurons in medial PFC during postnatal development. Furthermore, initiation of Cyp26b1 expression in neonatal PFC depends on the connections between the thalamus and the neocortex. Thus, the thalamus has a postnatal role in regulating PV neuron development in PFC by inducing Cyp26b1 and thereby restricting retinoic acid signaling. Prenatally, the lack of thalamic input causes an aberrant radial distribution of medial ganglionic eminence-derived interneurons throughout the cortex. Therefore, the thalamus controls PV neuron development in PFC both by region-specific and cortex-wide mechanisms.