Multiple embryonic origins of nitric oxide synthase-expressing GABAergic neurons of the neocortex.

Lorenza Magno,Mariusz Mucha,Anna N Rubin,Nicoletta Kessaris,Marcio G Oliveira

doi:10.3389/fncir.2012.00065

Abstract

Cortical GABAergic interneurons in rodents originate in three subcortical regions: the medial ganglionic eminence (MGE), the lateral/caudal ganglionic eminence (LGE/CGE), and the preoptic area (POA). Each of these neuroepithelial precursor domains contributes different interneuron subtypes to the cortex. Neuronal NOS (nNOS)-expressing neurons represent a heterogenous population of cortical interneurons. We examined the development of these cells in the mouse embryonic cortex and their abundance and distribution in adult animals. Using genetic lineage tracing in transgenic mice we find that nNOS type I cells originate only in the MGE whereas type II cells have a triple origin in the MGE, LGE/CGE, and POA. The two populations are born at different times during development, occupy different layers in the adult cortex and have distinct neurochemical profiles. nNOS neurons are more numerous in the adult cortex than previously reported and constitute a significant proportion of the cortical interneuron population. Our data suggest that the heterogeneity of nNOS neurons in the cortex can be attributed to their multiple embryonic origins which likely impose distinct genetic specification programs.

Highlights

The gaseous biological messenger nitric oxide (NO) was originally described as a vasodilator (Furchgott and Zawadzki, 1980; Palmer et al, 1987) and has since been implicated in a variety of physiological processes
We could not determine whether this represented the true onset of neuronal NO synthase (NOS) (nNOS) expression or the timing of appearance of type II cells because at earlier stages the strong nNOS signal in the cortical plate may have masked any weak expression in interneurons
The barrel-like nNOS immunolabeling in layer IV may correspond to staining in the barrel centers, which are formed by afferents from the thalamus, or the barrel walls, which contain layer IV neurons

Summary

Introduction

The gaseous biological messenger nitric oxide (NO) was originally described as a vasodilator (Furchgott and Zawadzki, 1980; Palmer et al, 1987) and has since been implicated in a variety of physiological processes. NNOS cortical neurons have been subdivided into two types according to the intensity of NOS/NADPHd staining: heavily labeled type I neurons that have large somata, and weakly labeled type II cells that have smaller somata (Hashikawa et al, 1994; Yan et al, 1996; Smiley et al, 2000; Lee and Jeon, 2005). The two types of nNOS neurons have distinct but overlapping distributions within the cortex (Hashikawa et al, 1994; Kubota et al, 1994; Yan et al, 1996; Gonchar and Burkhalter, 1997; Smiley et al, 2000; Gotti et al, 2005; Lee and Jeon, 2005)

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Conclusion