Origin of GABAergic neurons in the human neocortex

  title={Origin of GABAergic neurons in the human neocortex},
  author={Kresimir Letinic and Roberto Zoncu and Pasko Rakic},
The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons. Projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons are inhibitory, containing GABA. The complex function of neocortical circuitry depends on the number and diversity of GABAergic (γ-aminobutyric-acid-releasing) local circuit neurons. Using retroviral labelling in organotypic slice cultures of the embryonic human forebrain, we demonstrate the… 
Subcortical origins of human and monkey neocortical interneurons
It is proposed that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon, and this work reveals that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping the understanding of the origin and classification ofPrimate neocortex.
The origins of cortical interneurons: mouse versus monkey and human.
In the course of evolution of the higher primate cortex, it is likely that new forms of cortical interneuron with origins in the ventricular neuroepithelium have been added to an older population derived from the ganglionic eminence.
Interneurons in the developing human neocortex
The findings from cryosections and previous in vitro results suggest that cortical interneuron progenitor population is more complex in humans relative to rodents, and the increased complexity of progenitors is probably evolutionary adaptation necessary for development of the higher brain functions characteristic to humans.
Multiple origins of human neocortical interneurons are supported by distinct expression of transcription factors.
The results suggest the existence of several categories of dorsal interneuronal progenitors in the human neocortical VZ/SVZ, in addition to ventrally derived corticalinterneurons described in rodents, which may underlie human brain's higher complexity and capacity to process information.
Spatio-temporal extension in site of origin for cortical calretinin neurons in primates
It is proposed that the primate caudal ganglionic eminence (CGE) could be the main source of calretinin interneurons for the posterior and lateral cortical regions, but not for the frontal cortex.
The Embryonic Preoptic Area Is a Novel Source of Cortical GABAergic Interneurons
It is shown that another subpallial structure, the preoptic area, is a novel source of cortical GABAergic interneurons in the mouse, and in utero labeling and genetic lineage-tracing experiments demonstrate that neurons born in this region migrate to the neocortex and hippocampus, where they differentiate into a distinct population of GABAergicInterneuron with relatively uniform neurochemical, morphological, and electrophysiological properties.
Origins of Cortical GABAergic Neurons in the Cynomolgus Monkey
The dorsal telencephalic origin of cortical GABAergic neurons is not human-specific but appears as a former event in the ascent of evolution that could provide GABAergic neurons to an expending neocortex.
Mechanisms regulating GABAergic neuron development
Similarities and differences in the molecular regulatory mechanisms reveal the core determinants of a GABAergic neuron as well as provide insights into generation of the vast diversity of these neurons.
Individual human cortical progenitors can produce excitatory and inhibitory neurons
Molecular barcoding is used to show that progenitor cells in the human cortex can produce both excitatory neurons and inhibitory interneurons, with implications for the understanding of the evolution of the human brain.
Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor cells in the subventricular zone.
The data suggest that NEX-positive progenitors within the SVZ are committed to a glutamatergic neuronal fate and have evolved to expand the number of cortical output neurons that is characteristic for the mammalian forebrain.


Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis.
Evidence is presented that retroviral-mediated expression of DLX2 in neocortical cells can induce GABAergic interneuron differentiation and the Dlx homeobox genes, which are essential for basal ganglia differentiation, are also required for the development of neocorticals and olfactory bulb interneurons.
Multipotent Stem Cells from the Mouse Basal Forebrain Contribute GABAergic Neurons and Oligodendrocytes to the Cerebral Cortex during Embryogenesis
Data indicate that the developing cerebral cortex incorporates both neuronal and glial products of basal forebrain and suggest that these immigrant cells arise from a common progenitor, a dlx-negative basal fore brain stem cell.
Specification of cerebral cortical areas.
The radial unit model provides a framework for understanding cerebral evolution, epigenetic regulation of the parcellation of cytoarchitectonic areas, and insight into the pathogenesis of certain cortical disorders in humans.
GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia
  • D. Lewis
  • Psychology, Biology
    Brain Research Reviews
  • 2000
The Medial Ganglionic Eminence Gives Rise to a Population of Early Neurons in the Developing Cerebral Cortex
It is shown that a substantial proportion of neurons of the marginal zone, including cells with features of Cajal-Retzius cells, and of the subplate and lower intermediate zone are not born in the ventricular neuroepithelium but instead originate in the medial ganglionic eminence (MGE), the pallidal primordium.
Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression.
Using Svet1 and Otx1 as cell-type-specific molecular markers for the upper and deep cortical layers, it is concluded that the Sey mutation affects predominantly the differentiation of the SVZ cells that fail to migrate into the cortical plate.
Mash1 regulates neurogenesis in the ventral telencephalon.
Mash1 is an important regulator of neurogenesis in the ventral telencephalon, where it is required both to specify neuronal precursors and to control the timing of their production.
Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex.
It is suggested that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.
Neurochemical compartmentation of monkey and human visual cortex: similarities and variations in calbindin immunoreactivity across species.
It is concluded that for layer III of primary visual cortex, a similar pattern of neuronal chemistry exists across species of primates which is related to this layer's compartmental organization.
Neuronal migration, with special reference to developing human brain: a review.