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Publication : Quantitative organization of neurotransmitters in the deep cerebellar nuclei of the Lurcher mutant.

First Author  Sultan F Year  2002
Journal  J Comp Neurol Volume  452
Issue  4 Pages  311-23
PubMed ID  12355415 Mgi Jnum  J:126831
Mgi Id  MGI:3762079 Doi  10.1002/cne.10365
Citation  Sultan F, et al. (2002) Quantitative organization of neurotransmitters in the deep cerebellar nuclei of the Lurcher mutant. J Comp Neurol 452(4):311-23
abstractText  The Lurcher mutant mouse is characterized by a primary selective loss of Purkinje cells, leading to the near total apoptotic death of these neurons. In contrast to the subsequent massive secondary degeneration of the granule cells and the inferior olivary neurons, only mild degeneration occurs in the deep cerebellar nuclei (DCN). However, it is not known to what extent the different populations of DCN neurons-glutamatergic principal projection neurons, gamma-aminobutyric acid (GABA)-ergic inferior olivary projection neurons, and glycinergic neurons-are affected in their neurotransmitter composition. To answer this question we studied the neurotransmitter contents (glutamate, GABA, and glycine) of DCN neurons and the size of synaptic boutons immunohistochemically on serial semithin sections in both Lurcher and wild-type mice. Applying the physical dissector counting method, our results confirmed the mild degeneration (a reduction by 20%) of large glutamatergic neurons and a more pronounced degeneration of GABAergic (by 42%) and glycinergic neurons (by 45%). On the other hand, an analysis of neurons colabeled for both GABA and glycine, revealed that this specific colabeling increased in the Lurcher mutant (by 40%). In addition, both the GABA-immunolabeled (IL) (by 56%) and the glycine-IL (by 45%) synaptic boutons showed an increase in diameter in the mutant. The density of these boutons showed a decrease of 30% each. In summary, the increase in the number of neurons colabeled for GABA and glycine, together with the increase in the size of the inhibitory synaptic boutons, could help in providing the minimum inhibition needed to maintain a residual 'cerebellar' functionality in the Lurcher DCN.
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