Perspectives on the Developmental Origins of Cortical Interneuron Diversity

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Cortical GABAergic interneurons in mice are largely derived from the subpallium. Work from our laboratory and others over the past five years has demonstrated that a developmental logic in space and time underlies the emergence of specific cortical interneuronal subtypes. Following on from the seminal work of the Rubenstein laboratory, we set out to fate map the output of the subpallial ganglionic eminences. Our initial approach utilized ultrasound backscatter microscopy to perform homotopic and heterotopic transplants of genetically marked progenitors from the lateral, medial and caudal ganglionic eminences (LGE, MGE and CGE, respectively) to unmarked host brains. The LGE, at least in the context of our transplant studies, did not appear to generate cortical interneurons. By contrast, we found that that approximately eighty percent of cortical interneurons arise from the MGE, while the remaining twenty percent were generated by the CGE. Hence, the majority of interneuron subtypes, including all fast spiking parvalbumin-positive basket cells and somatostatin-positive martinotti cells appear to arise from the MGE. A more restricted set of cortical interneurons seems to be generated in the CGE, the majority of which are bipolar calretinin/VIP-positive interneurons. Complementing these results, we have recently demonstrated using inducible genetic fate mapping that the MGE produces specific cortical interneuron subtypes at discrete timepoints during development. These studies demonstrate that cortical interneurons arise from a precise developmental programme that acts in both space and time. Beyond this however, it seems likely that postmitotic events influence the specific function of subclasses of cortical interneurons. A primary challenge in the future will be to investigate what aspects of interneuron diversity are determined by intrinsic genetic programmes within each lineage versus those properties imposed by the local environment in the cortex.

Original languageEnglish (US)
Title of host publicationCortical Development
Subtitle of host publicationGenes and Genetic Abnormalities
PublisherJohn Wiley and Sons Ltd.
Pages21-34
Number of pages14
ISBN (Electronic)9780470994030
ISBN (Print)9780470060926
DOIs
StatePublished - Feb 1 2008

Keywords

  • Cortical interneuron diversity and cortical interneurons origin
  • Integration and differentiation pattern
  • Intrinsic physiological properties
  • Lucifer yellow fill and immuno-visualization
  • Parvalbumin-positive basket cells and somatostatin-positive artinotti cells
  • Postnatal patch clamp analysis
  • Striatum and olfactory bulb neurons
  • Subpallial ganglionic eminences
  • Ultrasound backscatter microscopy
  • Ultrasound backscatter microscopy (UBM)-guided transplantation

ASJC Scopus subject areas

  • Immunology and Microbiology(all)

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  • Cite this

    Fishell, G. (2008). Perspectives on the Developmental Origins of Cortical Interneuron Diversity. In Cortical Development: Genes and Genetic Abnormalities (pp. 21-34). John Wiley and Sons Ltd.. https://doi.org/10.1002/9780470994030.ch3