Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum.
Synaptic transmission mediated by gamma-amino butyric acid (GABA) plays an important role in inhibition of glutamatergic excitatory transmission and expression of higher brain functions, such as memory, learning and anxiety. To elucidate mechanisms underlying formation of the postsynaptic elements for GABAergic transmission, we employed the reeler mutant mice in this study. In the reeler cerebellum, abnormal cytoarchitecture and an aberrant environment affect the formation of neural networks and maturation of neurons. We examined the expression and localization of GABA(A) receptor alpha subunits in the reeler cerebellum and determined whether various abnormalities in the reeler mice affected formation of the postsynaptic elements. In situ hybridization analysis revealed that the specific expression of alpha subunit mRNAs in each neuronal type was preserved. Abnormal expression of alpha subunits was not detected, although GABAergic networks were altered and neuronal maturation was severely disturbed. Immunohistochemistry for the alpha1 and alpha6 subunits, which were expressed abundantly in the reeler cerebellum, revealed that both subunit proteins accumulated at positions adjacent to GABAergic terminals. These results, taken together, suggested that expression of the GABA(A) receptor subunits in postsynaptic neurons might be genetically determined, but trafficking and accumulation of the subunit proteins at the GABAergic synapse may be induced by GABAergic innervation.
Takayama
Chitoshi
C
Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan. takachan@med.hokudai.ac.jp
Inoue
Yoshiro
Y
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000002:abnormalities / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid