Regional variations of cytochrome oxidase activity in the central auditory system of Relnrl-Orl (reeler) mutant mice.

Despite preserved cell differentiation, the Reln(rl-Orl) phenotype comprises laminar abnormalities of cell position in auditory cortex and dorsal cochlear nucleus. The metabolic consequences of the cell ectopias were determined by estimating cytochrome oxidase (CO) activity, a marker of neuronal activity. CO activity increased in the granular cell layer of dorsal cochlear nucleus, trapezoid body nucleus, intermediate lateral lemniscus, central and external inferior colliculus, and pyramidal cell layer of primary auditory cortex. On the contrary, CO activity decreased in the superficial molecular layer of dorsal cochlear nucleus as well as in the medioventral periolivary nucleus. These metabolic variations are discussed in terms of their possible relation to morphologic anomalies observed in the mutant.

Neurobehavioral evaluation of Reln-rl-orl mutant mice and correlations with cytochrome oxidase activity.

The Reln-rl-orl mutation is characterized by a marked deficit in cerebellar granule cell and Purkinje cell number as well as ectopias in cerebellum, hippocampus, and neocortex. By comparison to Balb/c controls, Reln-rl-orl mutants did not alternate spontaneously in a T-maze and were deficient for visuomotor guidance in a water maze. Despite cerebellar ataxia and motor coordination impairments on stationary beam, coat-hanger, and rotorod tests, the horizontal motor activity of Reln-rl-orl mutants was not reduced in an open-field. The elevated cytochrome oxidase (CO) activity in Purkinje cells and the reduced CO activity in the roof nuclei (interpositus and dentate) of the mutants were associated with poor performance on the small stationary beam. In addition, deficient CO activity of the granular layer of the motor cortex was associated with shorter latencies before falling from the larger stationary beam and a lower number of rears in the open-field. Conversely, elevated CO activity in the polymorphic layer of primary somatosensory cortex was congruent with higher latencies before falling from the same apparatus, indicating functional compensation.

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Exploration and motor activity in juvenile and adult rats exposed to hypergravity at 1.8 G during development: a preliminary report.

Pups from gestating rats exposed to hypergravity (1.8 G) or to normal gravity at the perinatal period were evaluated for motor activity, exploration and social interactions during juvenile and adult stages. By comparison to controls, the hypergravity group had shorter latencies before choosing a maze arm in a T-maze and a lower number of exploratory pokes in a hole board. During dyadic encounters, the hypergravity group had a lower number of self-grooming episodes and shorter latencies before crossing under the opposing rat. In contrast, no intergroup differences were observed during exploration of an elevated plus-maze and a light-dark box. These results indicate that exposure to 1.8 G during development appears to decrease exploratory tendencies in the hole board and fear-related responses in T-maze and social interaction tests.

Regional brain variations of cytochrome oxidase activity in Relnrl-orl mutant mice.

Cell malpositioning has been described in laminated structures of the spontaneous mutation, reeler, including the cerebellum, the hippocampus, and the neocortex. Despite the ectopic positions of different neuronal populations, the specificity of synaptic connections is maintained. The metabolic consequences of this form of neuropathology were examined in Reln(rl) mutant mice by quantitative measures of cytochrome oxidase (CO) activity, a mitochondrial enzyme essential for oxidative metabolism in neurons. Despite severe tissue disorganization but in line with the intact synaptic organization, the reeler mutation did not affect global metabolic activity of the laminated structures of the brain. CO activity, however, was altered in specific subregions of the cerebellum, hippocampus, and neocortex, as well as in septum and various brainstem (medial pontine, paramedial reticular, paragigantocellular reticular) regions anatomically related to these structures, attesting to large functional alterations in Reln(rl-orl) brain. Metabolic activity variations were also detected in the ventral tegmental area and ventral neostriatum of the mesolimbic dopaminergic pathway. The results are discussed and compared to the regional CO variations found in other ataxic mice, in regard to the structural defects, the integrity of the connections, and the mutation-specific effects.