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The origin and specification of cortical interneurons

Nature Reviews Neuroscience volume 7, pages 687–696 (2006)Cite this article

Key Points

  • In contrast to cortical projection neurons, many cortical interneurons originate in the subcortical forebrain. The primary origins of cortical interneurons in rodents appear to be the caudal and medial ganglionic eminences.

  • Neurochemically and physiologically distinct subgroups of cortical interneurons appear to have distinct places of origin. This finding and other evidence suggest that key aspects of interneuron subgroup fate determination occur in their places of origin.

  • Additional regions that might contribute to the generation of cortical interneurons include the lateral ganglionic eminence, the rostral migratory stream and the septal region. Whether these regions generate specific interneuron subgroups is unknown.

  • In contrast to rodents and ferrets, humans might generate most cortical interneurons in the cortical subventricular zone.

  • The specification of medial ganglionic eminence-derived interneurons depends on the transcription factor Nkx2.1. The crucial maintenance of Nkx2.1 expression during the period of interneuron genesis requires sonic hedgehog signalling.

  • Dlx1 and Dlx2 function to promote the initial migration of cortical interneuron progenitors in the subcortical telencephalon. Postnatally, Dlx1 continues to be expressed in a subset of cortical interneuron subgroups, including those expressing calretinin, in which it is cell-autonomously required for their survival.

  • A number of mouse mutants show phenotypes that include cortical interneuron deficits and behavioural abnormalities, and the abnormal function of cortical interneurons has been implicated in various human neuropsychiatric disorders. Efforts to link the molecular control of interneuron fate determination with the control of interneuron function (connectivity and physiology) are poised to uncover new pathologies of and treatments for important human diseases.

Abstract

GABA-containing interneurons are crucial to both the development and function of the cerebral cortex. Unlike cortical projection neurons, which have a relatively conserved set of characteristics, interneurons include multiple phenotypes that vary on morphological, physiological and neurochemical axes. This diversity, and the relatively late, context-dependent maturation of defining features, has challenged efforts to uncover the transcriptional control of cortical interneuron development. Here, we discuss recent data that are beginning to illuminate the origins and specification of distinct subgroups of cortical interneurons.

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Figure 1: Migration pathways of cortical interneuron subgroups from the ventral telencephalon.
Figure 2: Relative contributions of the MGE and CGE to cortical interneuron neurochemical subgroups.
Figure 3: The transcriptional regulation of cortical interneuron specification and differentiation.

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Acknowledgements

Our work is supported by grants from the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke, National Institutes of Health.

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Authors and Affiliations

  1. Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, 10021, USA

    Carl P. Wonders

  2. Department of Psychiatry, Weill Medical College of Cornell University, New York, 10021, USA

    Stewart A. Anderson

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Correspondence to Stewart A. Anderson.

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DATABASES

OMIM

autism

holoprosencephaly

schizophrenia

Glossary

Fate-mapping approaches

Experiments that are designed to determine the relationship between the origin or genetic make-up of a cell and its differentiated fate.

Telencephalon

The anterior-most region of the neural tube, consisting of the cerebral cortex, basal ganglia, hippocampus, septal nuclei and olfactory bulb.

Subpallium

The regions of the telencephalon ventral to the cerebral cortex, including the basal ganglia.

Parvalbumin

(PV). A calcium-binding protein that is localized to, and potentially acts as an endogenous buffer for, fast-spiking cortical interneurons.

Somatostatin

(SST). A neuropeptide that is localized to a subset of cortical interneurons.

Calretinin

(CR). A calcium-binding protein that is localized to a subset of cortical interneurons.

S-phase of the cell cycle

The phase of the cell cycle during which DNA replication takes place.

Bipolar cells

Small cells with narrow dendritic arborizations that extend vertically, often across the entire cortical thickness.

Martinotti cells

Cells containing axons that project towards cortical layer I, and that primarily target the distal-most dendrites of pyramidal neurons.

Holoprosencephaly

A developmental disorder caused by the failure of the forebrain to divide into bilateral hemispheres.

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Wonders, C., Anderson, S. The origin and specification of cortical interneurons. Nat Rev Neurosci 7, 687–696 (2006). https://doi.org/10.1038/nrn1954

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