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Cerebral Cortex, Vol. 13, No. 9, 932-942, September 2003
© 2003 Oxford University Press

Blockade of GABAB Receptors Alters the Tangential Migration of Cortical Neurons

Guillermina López-Bendito, Rafael Luján1, Ryuichi Shigemoto2, Paul Ganter3, Ole Paulsen3 and Zoltán Molnár

Department of Human Anatomy & Genetics, University of Oxford, Oxford OX1 3QX, UK, , 1 Centro Regional de Investigaciones Biomédicas, Facultad de Medicina, Universidad de Castilla, La Mancha, Campus Biosanitario, 02071 Albacete, Spain, , 2 Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, CREST Japan Science and Technology Corporation, Japan and , 3 University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK

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 (~98%) migrating through the lower intermediate zone (LIZ) on their way from the medial ganglionic eminence to the cerebral cortex, express GABABR1. Blockade of GABABRs 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 GABABR 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 GABABRs have an important modulatory role in the migration of cortical interneurons.


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