A Wide Diversity of Cortical GABAergic Interneurons Derives from the Embryonic Preoptic Area

Abstract

GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of cells that are crucial for cortical function. Different classes of interneurons specialize in targeting specific subcellular domains of excitatory pyramidal cells or other interneurons, which provides cortical circuits with an enormous capability for information processing. As in other regions of the CNS, cortical interneuron diversity is thought to emerge from the genetic specification of different groups of progenitor cells within the subpallium. Most cortical interneurons originate from two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that progenitors in the embryonic preoptic area (POA) also produce a small population of cortical GABAergic interneurons. Here, we show that the contribution of the POA to the complement of cortical GABAergic interneurons is larger than previously believed. Using genetic fate mapping and in utero transplantation experiments, we demonstrate that Dbx1-expressing progenitor cells in the POA give rise to a small but highly diverse cohort of cortical interneurons, with some neurochemical and electrophysiological characteristics that were previously attributed to MGE-or CGEderived interneurons. There are, however, some features that seem to distinguish POA-derived interneurons from MGE-or CGE-derived cells, such as their preferential laminar location. These results indicate that the mechanisms controlling the specification of different classes of cortical interneurons might be more complex than previously expected. Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse.

Principles of Current Vertebrate Neuromorphology

“…MGE, Dg, and PoA are all involved in the production of neocortical inhibitory interneurons ( Fig. 10 A), and it has been shown that the progenitor zones of each of these domains produce distinct interneuronal subtypes [Gelman et al, 2011;Ma et al, 2013;Puelles et al, 2016]. Neocortical inhibitory interneurons generated in the subpallium enter the pallium through two different routes, i.e., a deep path within the intermediate zone between the pallial matrix and the cortical plate, and a superficial trajectory within the marginal zone ( Fig.…”

Interneuron Transplantation as a Treatment for Epilepsy

“…Unlike glutamatergic projection neurons, which derive from proliferative regions in the dorsal telencephalon (Angevine and Sidman 1961;Rakic 1972;Tan et al 1998), cortical interneurons are largely born within distinct progenitor zones of the subcortical basal ganglia and populate the forebrain through long-distance tangential (nonradial) migration during late embryonic and early postnatal development Tamamaki et al 1997). In rodents and primates (Anderson et al 2001;Nery et al 2002;Hansen et al 2013;Ma et al 2013), including humans, the majority of cortical interneurons derive from two transitory regions of the ventral lateral ventricle in the embryonic telencephalon, the medial and caudal ganglionic eminences (MGEs and CGEs, respectively), with a smaller contribution from the preoptic area (POA) (Gelman et al 2011).…”

The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain

“…The migration of the POa-derived cells is poorly understood, although recently this population has been revealed to be the source of GABAergic In utero electroporation, E11.5 to E13.5 neurons in the neocortex and the amygdala (8)(9)(10). The present findings show that the POa-derived cells that were migrating to the neocortex and the amygdala initially shared the migratory stream and then took separate paths controlled by the dynamic expression of COUP-TFII and Nrp2.…”

“…Recent studies using Nkx5.1-Cre and Dbx1-Cre mice show the preoptic area (POa) as a new source of cortical GABAergic neurons containing an Lhx6-expressing population (8,9). Other investigators report that the POa supplies GABAergic neurons to the medial nucleus of amygdala, in a study using Dbx1-Cre knock-in mice (10).…”