Premium
Phenotype of cerebellar glutamatergic neurons is altered in stargazer mutant mice lacking brain‐derived neurotrophic factor mRNA expression
Author(s) -
Richardson Christine A.,
Leitch Beulah
Publication year - 2004
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20386
Subject(s) - cerebellum , biology , glutamatergic , neurotrophic factors , brain derived neurotrophic factor , granule cell , endocrinology , neuroscience , glutamate receptor , purkinje cell , medicine , microbiology and biotechnology , central nervous system , biochemistry , dentate gyrus , receptor
Brain‐derived neurotrophic factor (BDNF) influences neuronal survival, differentiation, and maturation. More recently, its role in synapse formation and plasticity has also emerged. In the cerebellum of the spontaneous recessive mutant mouse stargazer ( stg ) there is a specific and pronounced deficit in BDNF mRNA expression. BDNF protein levels in the cerebellum as a whole are reduced by 70%, while in the granule cells (GCs) there is a selective and near total reduction in BDNF mRNA expression. Recently, we published data demonstrating that inhibitory neurons in the cerebella of stgs have significantly reduced levels (∼50%) of γ‐aminobutyric acid (GABA) and fewer, smaller inhibitory synapses compared to wildtype (WT) controls. Our current investigations indicate that the stargazer mutation has an even more pronounced effect on the phenotype of glutamatergic neurons in the cerebellum. There is a profound decrease in the levels of glutamate‐immunoreactivity (up to 77%) in stg compared to WT controls. The distribution profile of presynaptic vesicles is also markedly different: stgs have proportionally fewer docked vesicles and fewer vesicles located adjacent to the active zone ready to dock than WTs. Furthermore, the thickness of the postsynaptic density (PSD) at mossy fiber‐granule cell (MF‐GC) and parallel fiber‐Purkinje cell (PF‐PC) synapses is severely reduced (up to 33% less than WT controls). The number and length of excitatory synapses, however, appear to be relatively unchanged. It is possible that at least some of theses changes in phenotype are directly attributable to the lack of BDNF in the cerebellum of the stg mutant. J. Comp. Neurol. 481:145–159, 2005. © 2004 Wiley‐Liss, Inc.