Perspectives on the Developmental Origins of Cortical Interneuron Diversity

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Gordon Fishell

Published Online: 1 FEB 2008

DOI: 10.1002/9780470994030.ch3

Cortical Development: Genes and Genetic Abnormalities: Novartis Foundation Symposium 288

Cortical Development: Genes and Genetic Abnormalities: Novartis Foundation Symposium 288

How to Cite

Fishell, G. (2008) Perspectives on the Developmental Origins of Cortical Interneuron Diversity, in Cortical Development: Genes and Genetic Abnormalities: Novartis Foundation Symposium 288 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470994030.ch3

Author Information

  1. NYU School of Medicine, Smilow Neuroscience Program and the Department of Cell Biology, 5th Smilow Bldg, 522 First Avenue, New York, NY 10016, USA

Publication History

  1. Published Online: 1 FEB 2008
  2. Published Print: 11 JAN 2008

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470060926

Online ISBN: 9780470994030

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Keywords:

  • subpallial ganglionic eminences;
  • ultrasound backscatter microscopy;
  • parvalbumin-positive basket cells and somatostatin-positive Martinotti cells;
  • cortical interneuron diversity and cortical interneurons origin;
  • intrinsic physiological properties;
  • ultrasound backscatter microscopy (UBM)-guided transplantation;
  • striatum and olfactory bulb neurons;
  • integration and differentiation pattern;
  • postnatal patch clamp analysis;
  • Lucifer yellow fill and immuno-visualization

Summary

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.