Electrophysiology and GABA-immunocytochemistry in the vestibular nuclei of normal (C57BL/6J) and Leaner mutant mice.
Neurological disorders of genetic origin that lead to distinct disarrangements of the cerebellar wiring and cause a specific motor behaviour are likely to differentially influence the response properties and activity of postsynaptic cerebellar target neurons in the deep cerebellar (DCN) and vestibular nuclei (VN). Comparative electrophysiological and morphological analyses of these neurons in different mutants may increase our understanding of the physiological consequences of cell damage to the cerebellum and help to elucidate the relationships between histopathology and severeness of motor impairment. The Leaner mutation removes GABAergic inhibitory input to the VN predominantly originating from Purkinje cells (PC) located in the anterior lobe of the cerebellum and causes extremely severe motor disability when compared to other cerebellar mutants. In the present study the electrophysiological properties of naturally stimulated (sinusoidal head and body rotation) neurons in the VN of Leaner mutants and their corresponding wild-types (C57BL/6J) were investigated. Neuronal activity of VN single units in Leaner mutants is significantly increased over that of wild-types (frequency range 0.2-0.6 Hz) and more pronounced for type I neurons than for type II. Phase relationships and spontaneous activity are similar at these frequencies in both groups. To elucidate the degree of GABAergic input loss of VN-neurons, quantitative morphometric and numerical analyses of GABA-immunopositive synaptic boutons in the lateral VN of Leaner mutants were performed in addition and revealed significantly smaller terminals and a massive decrease (80%) in Leaner mutant terminal numbers compared to controls. In the context of the findings recently obtained in Weaver and Purkinje cell degeneration (PCD) mutants, the results in Leaner suggest that the loss of inhibition due to the PC degeneration in the anterior vermis leads to a differential enhancement of type I and type II target neuron activity in the VN. The overall activity in Leaner is intermediate between PCD (no increase in activity) and Weaver (strong increase of type I but no increase of type II). GABA-immunocytochemistry supports the idea that in Leaner the lost GABAergic PC-innervation of the lateral VN has not been replaced by surviving PCs, which is in contrast to Weaver where sprouting of GABAergic terminals in this nucleus was observed. Substitution of lost cerebellar inhibition by non-cerebellar sources, as suggested in the case of PCD-mutants, is uncertain in Leaner due to the increased activity of type I target neurons. These conditions may contribute, among others, to the severe motor disturbances in Leaner.
Grüsser-Cornehls
U
U
Department of Physiology, Freie Universität Berlin, Germany.
Luy
M
M
Bäurle
J
J
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology*; D009411:Nerve Endings / Q000502:physiology; D012399:Rotation; D014726:Vestibular Nuclei / Q000737:chemistry / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D005680:gamma-Aminobutyric Acid