Origins of Cortical Interneuron Subtypes

By Qing Xu, I. Cobos, Estanislao Daniel De La Cruz, John L. Rubenstein, S. Anderson. Journal of Neuroscience, 2004

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Cerebral cortical functions are conducted by two general classes of neurons: glutamatergic projection neurons and GABAergic interneurons. Distinct interneuron subtypes serve distinct roles in modulating cortical activity and can be differentially affected in cortical diseases, but little is known about the mechanisms for generating their diversity. Recent evidence suggests that many cortical interneurons originate within the subcortical telencephalon and then migrate tangentially into the overlying cortex. To test the hypothesis that distinct interneuron subtypes are derived from distinct telencephalic subdivisions, we have used an in vitro assay to assess the developmental potential of subregions of the telencephalic proliferative zone (PZ) to give rise to neurochemically defined interneuron subgroups. PZ cells from GFP+ donor mouse embryos were transplanted onto neonatal cortical feeder cells and assessed for their ability to generate specific interneuron subtypes. Our results suggest that the parvalbumin- and the somatostatin-expressing interneuron subgroups originate primarily within the medial ganglionic eminence (MGE) of the subcortical telencephalon, whereas the calretinin-expressing interneurons appear to derive mainly from the caudal ganglionic eminence (CGE). These results are supported by findings from primary cultures of cortex from Nkx2.1 mutants, in which normal MGE fails to form but in which the CGE is less affected. In these cultures, parvalbumin- and somatostatin-expressing cells are absent, although calretinin-expressing interneurons are present. Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants. By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/d221bd3ad6bbe237c7ad42a602693456a4145ad5

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Citations in the corpus

The Basal Forebrain Cholinergic Projection System in Mice Neuron Types in the Basal Forebrain - Chapter 28 The Mouse Nervous System (2012, background): “Whereas much is known about the specification of cortical interneurons and projection neurons (Merot et al., 2009; Suter et al., 2007; Wonders and Anderson, 2006; Xu et al., 2004), data are only slowly emerging relating to the basal forebrain cholinergic system.”
The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors (2010, background): “Of this population, as much as 60% have been traditionally thought to be FS neurons (Xu et al., 2004; Butt et al., 2005; Gonchar et al., 2007).”
Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex (2005, methodology): “Neocortex was pooled from four or eight embryos and dissociated with 0.05% trypsin as described previously (Xu et al., 2004).”
Three Groups of Interneurons Account for Nearly 100% of Neocortical GABAergic Neurons (2011, methodology): “The two most studied groups of interneurons (PV and SST expressing) are derived exclusively from the MGE (Xu et al., 2004; Fogarty et al., 2007; Miyoshi et al., 2007).”
The origin and specification of cortical interneurons (2006, methodology): “In sum, the current data support a minor contribution from the LGE to the cortical interneuron population, which does not seem to include the SST- or PV-expressing subgroups ( Xu et al. 2004 ).”