Satb2regulates pyramidal cell differentiation and the development of feedforward inhibitory circuits in CA1 hippocampus

Abstract

SUMMARYIn CA1 hippocampus, pyramidal cells (PCs) can be separated into two classes, deep or superficial, based on their radial position. In mice, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. The molecular mechanisms that control PC differentiation and integration into hippocampal circuits remain unknown. Using mice, we found that the transcriptional regulator SATB2 is expressed in superficial PCs but absent from deep PCs at birth. Next, we conditionally knocked out (cKO)Satb2from PCs during early development and then investigated inhibitory circuits using whole-cell recordings in acute slices from juveniles. InSatb2cKO mice, feedforward inhibition of superficial PCs increased to match that observed in deep PCs. In paired recordings between PCs and PV+ interneurons, we found increased strength of inhibitory synapses selectively to superficial PCs. This was due to increased density of perisomatic PV+ synaptic puncta. Thus,Satb2expression in superficial PCs suppresses PV+ interneuron synapse formation to establish differential feedforward inhibition in CA1 hippocampus.