Neurotransmitters and brain maturation: Early paracrine actions of GABA and glutamate modulate neuronal migration

Migration of neurons from their birthplace to their final destination is an extremely important step in brain maturation, and cortical migration disorders are the most common brain developmental alteration observed in human patients. Among the mechanisms that govern neuronal migration, the neurotransmitters GABA and glutamate deserve particular attention: 1) neurotransmitters and receptors are expressed early in the developing brain, 2) neurotransmitters may act as paracrine signaling molecules in the immature brain, and 3) neurotransmitters regulate intracellular calcium required for many cellular functions, including cytoskeletal dynamic changes. Thus, many reports reviewed here aimed to demonstrate that the activation of specific GABA and glutamate receptors is instrumental in cell migration by acting as motility promoting, acceleratory, or stop signal. Interestingly, the regulation of migration by neurotransmitters and receptors depends on the type of migration (radial, tangential, or chain migration), the type of cells (principal glutamatergic neurons vs. GABAergic interneurons), and the brain area (neocortex, cerebellum, rostral migratory stream). A hypothesis is proposed that these differential actions in different cell types arise from a homeostatic-like regulation that controls final position, timing, and number of cells at destination.