Development of synaptic inhibition in glycine transporter 2 deficient mice.
Mice deficient for the neuronal glycine transporter subtype 2 (GlyT2) die during the second postnatal week after developing neuromotor deficiencies, which resembles severe forms of human hyperekplexia. This phenotype has been attributed to a dramatic reduction in glycinergic neurotransmission. In the present study we analyzed the development of GABAergic and glycinergic synaptic transmission in GlyT2-knockout mice during early postnatal life. Anti-glycine immunohistochemistry in spinal cord and brainstem slices and whole-cell voltage-clamp recordings of glycinergic inhibitory postsynaptic currents (IPSCs) from hypoglossal motoneurons revealed strikingly reduced levels of synaptic glycine already at birth. Since GABA and glycine use the same vesicular inhibitory amino acid transporter (VIAAT or VGAT) we also analysed GABAergic neurotransmission. No increase of GABA immunoreactivity was observed in the spinal cord and brainstem of GlyT2(-/-) mice at any stage of postnatal development. Correspondingly no up-regulation of GABAergic IPSCs was detected in GlyT2(-/-) hypoglossal motoneurons. These data suggest that in the first postnatal week, loss of the glycine transporter 2 is neither compensated by glycine de-novo synthesis nor by up-regulation of the GABAergic transmission in GlyT2(-/-) mice.
Latal
A Tobias
AT
Dept. Neuro- and Sensory Physiology, Center Physiology and Pathophysiology, Georg-August-University Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany.
Kremer
Thomas
T
Gomeza
Jesús
J
Eulenburg
Volker
V
Hülsmann
Swen
S
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000502:physiology*; D007002:Hypoglossal Nerve / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D050487:Glycine Plasma Membrane Transport Proteins; C493270:Slc6a5 protein, mouse; D005680:gamma-Aminobutyric Acid; D005998:Glycine