PT  - JOURNAL ARTICLE
AU  - James E. Crandall
AU  - Deirdre M. McCarthy
AU  - Kiyomi Y. Araki
AU  - John R. Sims
AU  - Jia-Qian Ren
AU  - Pradeep G. Bhide
TI  - Dopamine Receptor Activation Modulates GABA Neuron Migration from the Basal Forebrain to the Cerebral Cortex
AID  - 10.1523/JNEUROSCI.5124-06.2007
DP  - 2007 Apr 04
TA  - The Journal of Neuroscience
PG  - 3813--3822
VI  - 27
IP  - 14
4099  - http://www.jneurosci.org/content/27/14/3813.short
4100  - http://www.jneurosci.org/content/27/14/3813.full
SO  - J. Neurosci.2007 Apr 04; 27
AB  - GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance.