Blockade of GABA(B) receptors alters the tangential migration of cortical neurons.
To better understand the role of neurotransmitter receptors in neuronal differentiation and maturation a detailed knowledge of their identity, location and function in the plasma membrane of specific neuronal populations during development is required. Combining pre-embedding immunocytochemistry with cell tracking in embryonic brain slice cultures we show that virtually all neurons (approximately 98%) migrating through the lower intermediate zone (LIZ) on their way from the medial ganglionic eminence to the cerebral cortex, express GABA(B)R1. Blockade of GABA(B)Rs with a specific antagonist, CGP52432, resulted in a concentration-dependent accumulation of these tangentially migrating neurons in the ventricular/sub-ventricular zones (VZ/SVZ) of the cortex and fewer cells were observed in the cortical plate/marginal zone (CP/MZ) and LIZ. Moreover, they had significantly shorter leading processes compared with similar migrating cells in control slices. Electrophysiological recording in LIZ and CP cells revealed no direct effect of either CGP52432 or the GABA(B)R agonist, baclofen, on resting membrane properties suggesting that the effect of CGP52432 on migration might be mediated through a metabotropic action or the regulation of release of factors controlling migration. These results suggest that GABA(B)Rs have an important modulatory role in the migration of cortical interneurons.
López-Bendito
Guillermina
G
Department of Human Anatomy & Genetics, University of Oxford, Oxford OX1 3QX, UK. guillermina.lopez.benedito@anat.ox.ac.uk
Luján
Rafael
R
Shigemoto
Ryuichi
R
Ganter
Paul
P
Paulsen
Ole
O
Molnár
Zoltán
Z
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D002552:Cerebral Ventricles / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*
D001596:Benzylamines; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C083008:CGP 52432; D001418:Baclofen