The structural organization of neural circuits is strongly influenced by experience, but the underlying mechanisms are incompletely understood. We found that, in the developing dentate gyrus (DG), excitatory drive promotes the somatic innervation of principal granule cells (GCs) by parvalbumin (PV)-positive basket cells. In contrast, presynaptic differentiation of GCs and interneuron subtypes that inhibit GC dendrites is largely resistant to loss of glutamatergic neurotransmission. The networks of PV basket cells in the DG are regulated by vesicular release from projection entorhinal cortical neurons and, at least in part, by NMDA receptors in interneurons. Finally, we present evidence that glutamatergic inputs and NMDA receptors regulate these networks through a presynaptic mechanism that appears to control the branching of interneuron axons. Our results provide insights into how cortical activity tunes the inhibition in a subcortical circuit and reveal new principles of interneuron plasticity.
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