Common origins of hippocampal ivy and nitric oxide synthase expressing neurogliaform cells

GABAergic interneurons critically regulate cortical computation through exquisite spatio-temporal control over excitatory networks. Precision of this inhibitory control requires a remarkable diversity within interneuron populations that is largely specified during embryogenesis. Although nNOS+ interneurons constitute the largest hippocampal interneuron cohort their origin and specification remain unknown. Thus, as neurogliaform (NGC) and Ivy cells (IvC) represent the main nNOS+ interneurons we investigated their developmental origins. Although considered distinct interneuron subtypes NGCs and IvCs exhibited similar neurochemical and electrophysiological signatures including NPY expression and late-spiking. Moreover, lineage analyses, including loss-of-function experiments and inducible fate-mapping, indicated that nNOS+ IvCs and NGCs are both derived from medial ganglionic eminence (MGE) progenitors under control of the transcription factor Nkx2-1. Surprisingly, a subset of NGCs lacking nNOS arises from caudal ganglionic eminence (CGE) progenitors. Thus, while nNOS+ NGCs and IvCs arise from MGE progenitors, a CGE origin distinguishes a discrete population of nNOS-NGCs.