Temporal and spatial regulation of interneuron distribution in the developing cerebral cortex--an in vitro study.

GABAergic interneurons are local circuit cells that control the excitatory balance in most regions of the nervous system, particularly the cerebral cortex. Because they are integrated in every cortical module, we posed the question whether interneuronal precursors would display some topographic specificity between their origin at the ventral telencephalon and their cortical location after migration. If this was true, GABAergic cells would have to be provided with intrinsic features that would make them able to perform specific functional roles in each specific module. On the other hand, if no topography was found, one would conclude that inhibitory precursors would be functionally naive, being able to integrate anywhere in the cortex, with equal capacity of performing their functions. This issue was approached by use of organotypic cultures of wild mice embryonic slices, into which fragments of the ganglionic eminence taken from enhanced green fluorescent protein (eGFP) mice were implanted, observing the topographic location of both the implant and its destination. Despite the existence of different genetic domains in the ventricular zone of the medial ganglionic eminences (MGE), we found that cells originating in different regions spread in vitro all over the mediolateral axis of the developing cortical wall, independently of their sites of origin. Results favor the hypothesis that GABAergic precursors are functionally naive, integrating into modules irrespective of which cortical area they belong to.

Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections.

Members of the semaphorin family have been implicated in mediating axonal guidance in the nervous system by their ability to collapse growth cones and to function as chemorepellents. The present findings show that recombinant Semaphorin D has similar effects on cortical axons and, in addition, inhibits axonal branching. In contrast, semaphorin E acts as an attractive guidance signal for cortical axons. Attractive effects were only observed when growth cones encountered increasing concentrations or a patterned distribution of Semaphorin E, but not when they are exposed to uniform concentrations of this molecule. Specific binding sites for Semaphorin D and Semaphorin E were present on cortical fibers both in vitro and in vivo at the time when corticofugal projections are established. In situ hybridization analysis revealed that the population of cortical neurons used in our experiments express neuropilin-1 and neuropilin-2, which are essential components of receptors for the class III semaphorins. Moreover, semD mRNA was detected in the ventricular zone of the neocortex whereas semE mRNA was restricted to the subventricular zone. Taken together, these results indicate that semaphorins are bifunctional molecules whose effects depend on their spatial distribution. The coordinated expression of different semaphorins, together with their specific activities on cortical axons, suggests that multiple guidance signals contribute to the formation of precise corticofugal pathways.

Ontogenesis of lateralized rotational behavior in hamsters: a time series study.

This is a longitudinal study of the postnatal development of lateralized rotational behavior. Hamsters (n = 75) were tested for spontaneous rotational behavior in cylindrical arenas, from P2 (P1 = day of birth) to P60. A daily laterality index was calculated for each animal, of which the averages and standard deviations were used to follow the animals' lateralized behavior. A strong variability between and within animals appeared throughout development, with a tendency to the right side in most animals, which declined after the first postnatal week. No oscillatory cycles were identified. To study patterns of development, the series were divided into four periods and the animals were separated into five groups. The laterality indexes of all four periods were significantly different between the groups. A total of 79% of the animals showed consistent behavior along development: either a preference to one side (20% left, 26% right), or no preference at all (33%). The remaining animals changed preference during development. Only a few animals remained strongly lateralized throughout the 60 days, most of them showing a slight, non-significant preference after P10. Results suggest an ontogenetic decrease in lateralization of this behavior that could in part be explained by the maturation of an interhemispheric regulatory system.

Lateralization of rotational behavior in developing and adult hamsters.

Rotational asymmetries were studied in developing and adult hamsters, and compared to verify if early lateralization is a predictor of the animals' later performance. Animals were divided into two groups: group I (GI) was tested from P46 (P1 = day of birth) to P62, and group II (GII) was tested daily from P2 to P60. They were placed in a cylindric arena for 5 min under video recording, and their 90 degree right and left displacements were counted and normalized. Since adult animals of both groups did not differ significantly in the distribution of asymmetries, the data were pooled together: 38.8% were non-lateralized (NL), 39.4% were right-rotators (RR), and 21.8% were left-rotators (LR). No significant difference was discerned between males and females. Distribution of asymmetries in GII animals between P2 and P10 showed a predominance of lateralized (64.7% RR and 21.5% LR) over NL animals (13.8%). The proportion of pups that maintained their classification into adulthood was only 46%, and the kappa coherence coefficient for these data was only 0.09. We conclude that: (1) most adults are lateralized, RR being more frequent; (2) the proportion of lateralized adults is not significantly altered by early testing; (3) there is no significant difference between males and females; (4) most developing hamsters are lateralized, right-rotators being more frequent; and (5) the animals' early classification is not a good predictor of their preference as adults.

Bicommissural neurones in the cerebral cortex of developing hamsters.

The trajectory, developmental time course, and origin of callosal fibres that recross through the anterior commissure were studied in developing hamsters, using carbocyanines in fixed brains on different ages. The bicommissural fibres were found in hamsters from E15 through P7, but disappeared after P7. By double labelling it was found that the neurones of origin of these bicommissural fibres were located in the lateral cortex within the region where the callosal zone of origin overlaps that of the anterior commissure. From these experiments, it was concluded that the axons of a group of cells in the lateral cortex of developing rodents are branched and grow transiently through both the callosum and the anterior commissure.