Enlargement of GAD-immunopositive terminals in the

Reorganization of cerebellar circuitry due to specific cell loss in Weaver mutants causes physiological and morphological alterations in the terminal domains of the GABAergic cerebellar corticovestibular projections. In this study sizes of anti-GAD immunopositive terminals in the dorsal part of the lateral vestibular nucleus (dLVN) of normal mice and Weaver mutants were quantified morphometrically. In anti-GADimmunoreacted material terminal sizes in the dLVN of Weaver exceed significantly those of coprocessed wildtypes. This suggests that the cerebellar disturbances in Weaver predispose the normal synaptic remodelling observed in wildtypes towards the formation of enlarged terminals

The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice

Ataxia represents a pathological coordination failure that often involves functional disturbances in cerebellar circuits. Purkinje cells (PCs) characterize the only output neurons of the cerebellar cortex and critically participate in regulating motor coordination. Although different genetic mutations are known that cause ataxia, little is known about the underlying cellular mechanisms. Here we show that a mutated ax(J) gene locus, encoding the ubiquitin-specific protease 14 (Usp14), negatively influences synaptic receptor turnover. Ax(J) mouse mutants, characterized by cerebellar ataxia, display both increased GABA(A) receptor (GABA(A)R) levels at PC surface membranes accompanied by enlarged IPSCs. Accordingly, we identify physical interaction of Usp14 and the GABA(A)R alpha1 subunit. Although other currently unknown changes might be involved, our data show that ubiquitin-dependent GABA(A)R turnover at cerebellar synapses contributes to ax(J)-mediated behavioural impairment