Plasticity of GABAergic terminals in Deiters' nucleus of weaver mutant and normal mice: a quantitative light microscopic study

Abstract

This study reports on the developmental changes in size and the average density of GABAergic axonal boutons bordering on the somata of large neurons in the dorsal part of the lateral vestibular nucleus (Deiters' nucleus) in normal and mutant mice. Weaver mutants, PCD mutants and the corresponding wildtypes were used to test for size alterations and differences in the number of GABA-immunopositive terminals. Hemicerebellectomized animals were examined in addition. Quantification of bouton profile size was performed from 30-μm-thick vibratome and 0.5-μm Araldite-embedded semi-thin sections immunoreacted for GABA from 7 days postnatally up to an age of 9 months. Terminal density was determined at the 5–6 month stage from semi-thin sections only. Morphometric analysis over the lifetime of normal animals (B6CBA) revealed a progressive increase in the size of bouton profiles, which peaked at 5–6 months and reached sizes of 2–3 μm 2. In weaver mutants a parallel development in terminal size was found to be present, but the size of the largest terminals exceeded those of the controls by 75–100%, reaching 3–6 μm 2 with the same time course. PCD mutants, with an almost total absence of Purkinje cells had, on the contrary, small bouton profiles that reached a maximum of only 2 μm 2. The hemicerebellectomized animals responded with decreased bouton profile size ipsilaterally. The terminal numbers per unit membrane length were surprisingly similar in wildtypes and weaver mutants, despite a reduction in Purkinje cells of almost 50% in the weaver anterior lobe. In contrast, PCD mutants showed a drastic reduction of about 64% in GABAergic terminals contacting the large neurons in Deiters' nucleus. The results suggest a permanent reorganization in the size of GABAergic terminals of mainly cerebellar origin in Deiters' nucleus and provide evidence for sprouting of GABAergic terminals in the weaver mutant. Moreover the non-Purkinje cell GABAergic innervation of large Deiters' nucleus neurons is estimated to be ≃36%.