Metabotropic signaling within somatostatin interneurons regulates thalamocortical inputs during development.

During brain development, neural circuits undergo major activity-dependent restructuring. In contrast to other cortical neurons, somatostatin interneurons primarily receive strong thalamocortical inputs, which regress as the animals mature. Yet, the mechanisms underlying such transient connectivity are unknown. In contrast to other known connectivity, we found that transient thalamocortical inputs onto somatostatin interneurons is inversely correlated with postsynaptic neuron activity. Transient inputs recruit metabotropic mediated transcription supporting the later elimination of this connectivity, known to regulate the development of cortical networks. In particular, cell-type specific metabotropic glutamatergic receptor 1 regulates transcriptional levels of the guidance molecule, semaphorin 3A. Remarkably, we found that this developmental process impacts the development of normal exploratory behavior of adult mice. Synaptic maturation is usually thought to be activity-dependent and largely controlled presynaptically. However, our results indicate that thalamocortical afferents are regulated by negative metabotropic feedback from postsynaptic somatostatin cells and that this mechanism underlies the maturation of proper adult circuit functions.