Differential number of glycine‐ and GABA‐immunopositive neurons and terminals in the deep cerebellar nuclei of normal and Purkinje cell degeneration mutant mice

Abstract

The total number of glycine-immunopositive (Gly+) neurons in the deep cerebellar nuclei (DCN) was quantified under normal conditions in wild-types (B6C3Fe) and compared with the Purkinje cell-deprived situation in Purkinje cell degeneration (PCD)-mutants by using an unbiased stereological method, the disector. In addition, the size and density of Gly+ terminals, the number of γ-aminobutyric acid immunopositive (GABA+) somata and the somatal colocalization of Gly and GABA were determined. In both wild-types and PCD mutants, Gly+ somata are distributed relatively homogeneously among the different subdivisions of the DCN. However, in the complete volume of the DCN, which is reduced in PCD mutants by 52%, 8,582 Gly+ neuronal somata are present in wild-types and 14,637 in PCD mutants, which corresponds to an increase of 70.5% in the mutant. In contrast, the total number of GABA+ somata is almost the same in wild-types (16,713) and in PCD mutants (15,339). The number of neurons that colocalize both Gly and GABA is again almost identical in wild-types (3,976) and PCD mutants (3,861). Moreover, the size and number of Gly+ terminals contacting DCN neurons of PCD mutants are increased significantly compared to the wild-types. These data define for the first time the normal distribution of glycine and its somatal colocalization with GABA in the DCN of the mouse. In addition, it is shown that the Purkinje cell loss in PCD mutants leads to a significant increase in Gly+ somata and to a larger size and number of Gly+ boutons in the DCN. This suggests that the respective neurons are capable of exerting an enhanced inhibitory synaptic activity on their target neurons, substituting, at least in part, for the lost Purkinje cell (PC) inhibition. Probable correlations of these findings with the mildness of the motor disturbances found in PCD mutants are discussed. J. Comp. Neurol. 382:443-458, 1997. © 1997 Wiley-Liss Inc.