Glial Glycine Transporter 1 Function Is Essential for Early Postnatal Survival but Dispensable in Adult Mice

The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying foxed GlyT1 alleles G1yT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knockout mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the G1yT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial G1yT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although G1yT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life. (C) 2010 Wiley-Liss, Inc.