The Cytokine CXCL12 Promotes Basket Interneuron Inhibitory Synapses in the Medial Prefrontal Cortex

Abstract

Prenatally, the cytokine CXCL12 regulates cortical interneuron migration, whereas its postnatal functions are poorly understood. Here, we report that CXCL12 is expressed postnatally in layer V pyramidal neurons and localizes on their cell bodies in the medial prefrontal cortex (mPFC), while its receptors CXCR4/CXCR7 localize to the axon terminals of parvalbumin (PV) interneurons. Conditionally eliminating CXCL12 in neonatal layer V pyramidal neurons led to decreased axon targeting and reduced inhibitory perisomatic synapses from PV+ basket interneurons onto layer V pyramidal neurons. Consequently, the mPFC of Cxcl12 conditional mutants displayed attenuated inhibitory postsynaptic currents onto layer V pyramidal neurons. Thus, postnatal CXCL12 signaling promotes a specific interneuron circuit that inhibits mPFC activity.

Keywords: CXCR4/CXCR7; axon targeting; layer V pyramidal neurons; parvalbumin interneurons; schizophrenia.