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.
Primate-Specific Origins and Migration of Cortical GABAergic Neurons
It is concluded that the development of cortical GABAergic neurons have exclusive features in primates that need to be considered in order to understand pathological mechanisms leading to some neurological and psychiatric diseases.
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.
Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity
It is shown here that the calcium-binding protein secretagogin (SCGN) is robustly expressed by neocortical GABAergic neurons derived from caudal ganglionic eminences and lateral ganglionics during human but not mouse brain development.
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.


GABAergic neurons and their role in cortical plasticity in primates.
  • E. Jones
  • Biology, Psychology
    Cerebral cortex
  • 1993
There is a potential mechanism for the plasticity of representational maps that is demonstrable in somatic sensory, motor, auditory, and visual cortex as well as in primate neocortex.
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.
Telencephalic origin of human thalamic GABAergic neurons
Modifications in the pattern of migratory guidance cues in the forebrain may underlie the appearance of a new migratory pathway and thus contribute to the evolutionary expansion of the thalamic association nuclei in the human.
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.