Robert Lalonde

Does the mutant mouse lurcher have deficits in spatially oriented behaviours

Lurcher mutant mice, in comparison to normal mice, had directional deficits in the Morris milk tank test and in a water-maze spatial alternation task. The lurcher mutants also showed an initial lack of spontaneous alternation and did not alternate in one behavioral condition when the inter-trial interval was lengthened. Lurcher mice were slower to learn a simple left/right position response to escape a T-maze by swimming although their motor coordination was good. Paradoxically, no deficit was observed in learning to select a left or right position for food in the same T-maze although the goal-directed locomotion was very ataxic. Overall, the lurcher mutants have difficulty in guiding themselves in the water toward a visible goal.

Cerebellar contributions to instrumental learning

There is emerging evidence that the cerebellum is involved in spatial and nonspatial instrumental learning tasks. Cerebellar-lesioned animals have deficits in water maze learning tasks that may be explained by two-way interactions with higher order brain regions. There is suggestive evidence that cerebellar modulation extends to shock avoidance and discrimination learning. Although this evidence needs to be confirmed by a wider range of lesion methods and choice of learning tasks, it is in line with the hypothesis that the cerebellum affects cognitive processes and is not strictly concerned with motor control and the acquisition and retention of conditioned reflexes.

Navigational deficits in weaver mutant mice

Weaver mutant mice have selective degeneration of cerebellar granule cells. In comparison to normal mice, the weaver mutants made more errors and took a longer time to reach a platform in a water-maze. Results are discussed in terms of a role for the cerebellum in spatial orientation.

Spontaneous alternation and habituation in a t-maze in nervous mutant mice.

Nervous mutant mice have a selective degeneration of Purkinje cells and deep cerebellar nuclei. In comparison with littermate controls, nervous mutant mice did not alternate spontaneously in a successive trial procedure (six consecutive trials per day) and did not habituate in a restricted part of a t-maze in a 4-min session. These data indicate that the cerebellum may have a role in spatial learning.

Absence of an association between motor coordination and spatial orientation in lurcher mutant mice

Lurcher mutant mice were impaired in spatial orientation and motor coordination in comparison to normal mice. Both groups improved across days in both invisible and visible water maze platform conditions. Contrary to normal mice, lurcher mutants did not improve over days in terms of the time taken to reach a side-bar in a motor coordination test, an indication of defective motor learning. However, lurchers were able to stay on the bar longer across days. These results indicate that motor learning deficits in this cerebellar-damaged animal are not absolute but dependent on the type of measurement attempted. There was no correlation between motor coordination and spatial orientation for normal mice. A similar absence of correlation was noted for lurcher mutants, except for falling latencies in the coat-hanger test during the middle of training.

Spontaneous alternation and habituation in Purkinje cell degeneration mutant mice.

Purkinje cell degeneration (pcd) mutant mice were found to be as active as normal mice in a T-maze. The pcd mutants, contrary to normal mice, did not alternate spontaneously in either a 2-trial or a 4-trial test. Results are discussed in terms of a role for the cerebellum in behavioral inhibition and visuo-spatial organization.

Exploration and habituation in Purkinje cell degeneration mutant mice.

Purkinje cell degeneration (pcd) mutant mice lose virtually all Purkinje cells. It was found that the pcd mutants did not show within-sessions habituation in terms of hole-poking responses. This type of perseverative responding has been found in rats with limbic system damage and implies a role for the cerebellum in behavioral inhibition.

Object exploration in staggerer mutant mice

Staggerer mutant mice, which lose Purkinje and granule cells in the cerebellum, were found to explore for a longer period of time than normal mice a novel object placed in a familiar environment. There was no difference between the two groups in terms of general motor activity. These results are discussed in regard to a role for the cerebellum in behavioral inhibition and emotion.

Delayed spontaneous alternation in weaver mutant mice.

Weaver mutant mice alternated above chance levels but less often than normal mice in a 2-trial spontaneous alternation test. When the inter-trial (or retention) interval was manipulated, the weaver mutants alternated above chance levels only at the shortest (15 s) but not at the longest (4 or 5 min) intervals, contrary to normal mice that alternated above chance levels at all 3 intervals. Results are discussed in terms of a role for the cerebellum in spatial working memory.

Elevated +-maze and hole-board exploration in lurcher mutant mice

The behavior of lurcher mice, a mutant with degeneration of cerebellar cells, was compared to that of normal mice for three days in two tests of exploration; an elevated (+)-maze and a 4 x 4 hole-board. In the elevated (+)-maze, lurcher mutants visited fewer closed arms than normal mice only on the first test day. Lurcher mutants were slower to emerge from the first closed arm but did not differ from normal mice for entry latencies into the first open arm. The time spent by the mutants in the open arms was higher than that of normal mice, an indication of decreased inhibition to open spaces. In the hole-board, lurcher mutants visited fewer holes than normal mice only on the first day of testing. In proportion to the total number of holes explored, lurcher mutants visited fewer center holes and fewer holes situated next to each other. These results may be due to a lesion-induced tendency to explore a more restricted region of a novel spatial environment and to explore it in a more haphazard fashion.