Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence

Verginia C. Cuzon, Pamela W. Yeh, Qing Cheng, Hermes H. Yeh

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

During corticogenesis, cells from the medial ganglionic eminence (MGE) migrate tangentially into the neocortical anlage. Here we report that γ-aminobutyric acid (GABA), via GABAA receptors, regulates tangential migration. In embryonic telencephalic slices, bicuculline produced an outward current in migrating MGE-derived cells in the neocortex, suggesting the presence of and tonic activation by ambient GABA. Ambient GABA was also present in the MGE, although this required demonstration using as bioassay HEK293 cells expressing high-affinity α6/β2/γ2s recombinant GABA A receptors. The concentration of ambient GABA was 0.5 ± 0.1 μM in both regions. MGE-derived cells before the corticostriate juncture (CSJ) were less responsive to GABA than those in the neocortex, and profiling of GABAA receptor subunit transcripts revealed different expression patterns in the MGE vis-à-vis the neocortex. These findings suggest a dynamic expression of GABAA receptor number or isoform as MGE-derived cells enter the neocortex and become tonically influenced by ambient GABA. Treatment with bicuculline or antibody against GABA did not affect migration of MGE-derived cells before the CSJ but decreased "crossing index," reflecting impeded migration past the CSJ into the neocortex. Treatment with diazepam or addition of exogenous GABA increased crossing index. We conclude that ambient GABA promotes cortical entry of tangentially migrating MGE-derived cells.

Original languageEnglish (US)
Pages (from-to)1377-1388
Number of pages12
JournalCerebral Cortex
Volume16
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Keywords

  • Corticogenesis
  • Developing neocortex
  • GABA receptor
  • GFP-MGE
  • Telencephalic slice coculture

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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