The Effect of Cerebellar Transplantation and Enforced Physical Activity on Motor Skills and Spatial Learning in Adult Lurcher Mutant Mice

Abstract

Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.

Dynamic Changes in the Cerebellar-Interpositus/Red-Nucleus-Motoneuron Pathway During Motor Learning

“…Recently, we have carried out a similar multiparametric study in wild-type and Lurcher mice also during classical eyeblink conditioning. As is known, Lurcher mice are devoid of Purkinje cells when >1 month of age [19][20][21][22].…”

“…Three different animal paradigms were used: alert behaving cats [11,12] and conscious wild-type and Lurcher mice [18]. As has been shown, Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance-including the acquisition of new motor abilities-because of the early postnatal degeneration of almost all of their Purkinje and granular cells [18][19][20][21][22]. The main outcome of this experimental approach is a more complete picture of events taking place simultaneously during the acquisition process, as well as a determination of nonlinear associations and putative temporal and/or causal relationships between recorded variables [23][24][25][26].…”

Cerebellum: links between development, developmental disorders and motor learning

“…Compensatory mechanisms occur also for genetically determined mutant mice such as Lurcher, which represents a natural model of olivocerebellar degeneration (Cendelín et al, 2009). They carry a mutation of the glutamate receptor delta2-subunit gene which is predominantly expressed by Purkinje neurons (Zuo et al, 1997).…”

Behavioral Characteristics, Associative Learning Capabilities, and Dynamic Association Mapping in an Animal Model of Cerebellar Degeneration

“…Lurcher mutants carry a spontaneous mutation in a gene coding for the GluR␦2 receptor, constituting a good model of cerebellar decortication, because adult individuals have no Purkinje cells (Caddy and Biscoe 1979;Cendelín et al 2008Cendelín et al , 2009Porras-García et al 2005;Vogel et al 2007;Yuzaki 2004;Zuo et al 1997). In the present study, we carried out the classical conditioning of eyelid responses with a delay paradigm in interpositus-lesioned and -nonlesioned wild-type and Lurcher mice.…”