Purkinje cell age-distribution in fissures and in foliar crowns: a comparative study in the weaver cerebellum

Abstract

Generation and settling of Purkinje cells (PCs) are investigated in the weaver mouse cerebellum in order to determine possible relationships with the fissuration pattern. Tritiated thymidine was supplied to pregnant females at the time that these neurons were being produced. Autoradiography was then applied on brain sections obtained from control and weaver offspring at postnatal (P) day 90. This makes it possible to assess the differential survival of neurons born at distinct embryonic times on the basis of the proportion of labeled cells located at the two foliar compartments: fissures and foliar crowns. Our data show that throughout the surface contour of the vermal lobes, generative programs of PCs were close between wild type and homozygous weaver. Similar data were found in the lobules of the lateral hemisphere. On the other hand, the loss of PCs in weaver cerebella can be related to foliar concavities or convexities depending on the vermal lobe or the hemispheric lobule studied. Lastly, we have obtained evidence that late-generated PCs of both normal and mutant mice were preferentially located in fissures. These quantitative relationships lead us to propose a model in which the final distribution of PCs through the vermal contour would be coupled to two factors: the cortical fissuration patterning and a "time-sequential effect" of weaver mutation.

GIRK2 and neuronal pattern of generation and settling in homozygous <em>weaver</em> mice

“…In the same rostrocaudal axis, PCs were also counted in both the fissures and the superficial (convex) areas of each cerebellar folium. 40 The names of lobes and lobules, as well as their limits, were those assigned by Altman and Bayer. 41 Criteria for scoring PCs included the presence of a large and clear nucleus, pear-shaped cell body, and their position between the molecular and granular cell layers.…”

“…Finally, another comparative study of PC generation and survival between +/+ and wv/wv mice was undertaken to determine possible relationships with the cerebellar fissuration pattern. 40 Separate analyses were carried out for each vermal lobe and hemispheric lobule at P90, with a distinction being made between fissures and foliar crowns. Our first observation was that in the grooves, as well as in the creases of every vermal lobe ( Figure 5) or hemispheric lobule (data not shown), the neurogenetic programs of weaver PCs closely resembled those of the wild-type group.…”

“…Several comparative studies about PC generation and settling in wild-type and homozygous weaver mice are reviewed here. 26,39,40,45,46 Separate analyses are carried out in sagittal sections, making a distinction between the mediolateral and anteroposterior cerebellar axes as well as between the two surface compartments of the cortex: fissures and…”

“…Consistent with early data from normal mouse cerebella, 54 an unbalanced age-distribution of PCs between fissures and foliar crowns has been found in both wild-type and mutant genotypes. 40 Moreover, although numerical depletion in weaver can be related to foliar concavities or convexities depending on the vermal lobe analyzed, the late-generated PCs are always preferentially located in fissures. We do not know why this occurs but, a priori, the PC developmental program should be taken into consideration.…”

Natural apoptosis in developing mice dopamine midbrain neurons and vermal Purkinje cells

“…Thus, whereas the timing and extent of dying PCs have been addressed [16], to our knowledge, no attempts have been made to determine whether physiological PC death is related to its time of origin. We know from previous autoradiographic studies that, in mice, cerebellar PCs are generated according to precise neurogenetic timetables [27,29]. Consequently, terminal deoxynucleotidyl transfe rasemediated dUTP nick end-labeling method (TUNEL) and [ 3 H]TdR autoradiography, and active caspase-3 immunohistochemistry and [ 3 H]TdR autoradiography were combined in the same tissue section to determine, at P4 and P7, if apoptotic PCs death in the region of the vermis is linked to their time of origin.…”