Cerebellar Golgi, Purkinje, and basket cells have reduced gamma-aminobutyric acid immunoreactivity in stargazer mutant mice.
The stargazer mutant mouse has characteristic ataxia and head-tossing traits coupled with a severe impairment in the acquisition of classical eye-blink conditioning (Qiao et al. [1996] J. Neurosci. 16:640-648; Qiao et al. [ 1998] J. Neurosci. 18:6990-6999). These phenotypes are thought to be cerebellar mediated and have been attributed to the specific reduction in brain-derived neurotrophic factor (BDNF). The granule cells in the cerebellum of the stargazer mouse exhibit a near-total and exclusive ablation of BDNF mRNA expression and a consequent defect in TrkB receptor signalling. To investigate whether the stargazer mutation and lack of availability of BDNF in the granule cells compromise the phenotype of the cerebellar inhibitory neurons, specifically their immunoreactivity for gamma-aminobutyric acid (GABA); the levels of GABA neurotransmitter expressed in Golgi, Purkinje, and basket cells; and the density of their synaptic contacts were compared in stargazer and wild-type controls using electron microscopy and quantitative immunogold labelling. The data presented in this study clearly show that, in the spontaneous ataxic mutant mouse stargazer, the cerebellar inhibitory neurons have significantly reduced levels of GABA immunoreactivity indicative of a significant decrease in their GABA content compared with wild-type controls. Furthermore, the density of inhibitory synapses between Golgi interneurons and granule cells and also between basket and Purkinje cells in stargazer mutants is reduced to approximately half that in wild-type controls. Whether this reduction in GABA content and inhibitory synapse density is directly attributable to the lack of BDNF in the cerebellum of the stargazer mutant is yet to be proved.
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D002524:Cerebellar Ataxia / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000648:ultrastructure*; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D011689:Purkinje Cells / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000235:genetics / Q000648:ultrastructure*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D005680:gamma-Aminobutyric Acid