Albert S. Berrebi

Corpus callosum: region-specific effects of sex, early experience and age

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.

Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig

SummaryThis investigation attempted to determine the mode of distribution and synaptic targets of the cartwheel cell axon in the guinea pig dorsal cochlear nucleus (DCoN). Antiserum against PEP-19, a putative calcium-binding neuropeptide, was employed at the light and electron microscopic levels. We show that in the hindbrain of the guinea pig, cerebellar Purkinje cells and DCoN cartwheel cells are the most densely immunoreactive neurons. The PEP-19 immunoreaction product is localized to all neuronal compartments of these cells. Primary targets of cartwheel cell axons are the DCoN pyramidal cells, the large efferent neurons of layer 2. These neurons receive numerous immunoreactive synaptic boutons on their cell bodies and apical and basal dendritic arbors. A PEP-19-immunoreactive axonal plexus, largely formed by cartwheel cell axons, highlights layer 3, co-extensively with the basal arbors of pyramidal cells. This plexus is oriented predominantly in the transstrial plane of the DCoN, in parallel with the sheetlike basal dendritic arbor of pyramidal neurons and with the isofrequency bands of primary cochlear nerve fibers. PEP-19-positive boutons contain pleomorphic synaptic vesicles and form symmetric synaptic junctions, indicative of inhibitory innervation. In addition, immunoreactive boutons, similar to those synapsing on pyramidal neurons, were observed on the cell bodies and main dendritic trunks of cartwheel neurons, indicating a system of recurrent collaterals. Furthermore, a small number of PEP-19-positive axons of unknown origin reach the caudal rim of the posteroventral cochlear nucleus. Within the territory of distribution of the cartwheel cell axon are the dendrites of at least two other types of DCoN neuron, the vertical cells of Lorente de Nó and the giant cells. These neurons may represent additional targets of the cartwheel cell axon, but this remains to be ascertained with specific methods. Our data demonstrate that the cartwheel neurons modulate the activity of pyramidal neurons and, therefore, play a key role in shaping the output of the DCoN superficial layers.

The Purkinje cell class may extend beyond the cerebellum

SummaryThe cerebellum develops from a germinal zone at the rhombic lip of the metencephalon. This region, like the telencephalic vesicle which gives rise to the cerebral cortex, presumably consists of germinative units showing a rather repetitive neurogenetic pattern. In all cerebellar folia, cortical neurons, and especially the Purkinje cells, express highly stereotyped phenotypes, although some variations in their chemical make-up have been uncovered with monoclonal antibodies. Here, we demonstrate for the first time that three independent murine mutations,Lurcher, Purkinje cell degeneration andstaggerer, which result in the postnatal degeneration of Purkinje cells, also cause the elimination of cartwheel cells of the dorsal cochlear nucleus. The cerebellar granule cell mutation,weaver, which spares most Purkinje cells in the lateral cerebellum, also spares cartwheel cells. These data support the notion that the cerebellar germinative zone extends to the caudal portion of the rhombic lip, which gives rise to the dorsal cochlear nucleus.

Prenatal testosterone causes shift of asymmetry in neonatal tail posture of the rat

Neonatal tail posture is a sexually dimorphic behavior with females more biased leftwards than males. Prenatal exposure of female pups to testosterone propionate (TP) but not dihydrotestosterone propionate (DHTP) shifts the population pattern of tail posture to the right. No effects were found with male pups. Since TP is aromatizable and DHTP is not, it is concluded that TP exerts its effects on tail posture via the CNS.

Effects of the murine mutation ‘nervous’ on neurons in cerebellum and dorsal cochlear nucleus

Summary‘Nervous’ mutant mice are presently available on two different genetic background strains which are derived from out-breeding of the original BALB/cGr mutant stock. Light and electron microscopic studies of these mutants demonstrate that cerebellar Purkinje cells and cartwheel neurons of the dorsal cochlear nucleus (DCoN) show similar, albeit not identical, cytoplasmic and mitochondrial alterations in both background strains.In the cerebellar cortex, all Purkinje cell perikarya developed a varying number of enlarged and rounded mitochondria, as previously described. Extensive changes were observed in various components of the mitochondrial matrix. As cellular degeneration proceeded, reduction, fragmentation and dilation of cisterns of endoplasmic reticulum and the Golgi apparatus were evident. Some of the mitochondria underwent a peculiar type of degeneration, i.e. the outer membrane partially or completely dissolved, occasionally accompanied by focal interruptions of the inner membrane. In older adult mutants only 10% of cerebellar Purkinje cells rehained. The few surviving cells displayed varying states, ranging from essentially normal ultrastructure to electron-dense condensation. Many of these cells, in both strains, continued to display greatly enlarged, rounded mitochondrial profiles, indicating a change in the expression of the gene defect resulting from genetic contamination.Criteria for the identification of neuronal cell classes in layers 1 and 2 of murine DCoN were established. Cartwheel neurons in the mutant DCoN presented alterations similar to those observed in cerebellar Purkinje cells. The characteristic mitochondrial anomaly developed and proceeded in cartwheel neurons within a comparable time frame. The vast majority of affected cartwheel cells did not undergo degeneration, however, but continued to possess altered mitochondria into adulthood. The differences between normal and mutant mitochondria in Purkinje and cartwheel cells were quantified by morphometric analyses.Our findings lend support to the notion of a homology between cerebellar Purkinje cells and DCoN cartwheel cells. These cells represent major elements in two similar spatially related circuits, and share several genetic, structural and neurochemical properties. It is therefore proposed that these two cell populations are derived from closely related precursor cells.

A factor analysis of the rat's corpus callosum*

Previous work from our laboratory (Berrebi et al., Brain Research, 438 (1988) 216-224) demonstrated region-specific sexual dimorphisms in the size of the rats corpus callosum, which are modifiable by extra stimulation in early life. These differences are assumed to reflect regional corticocortical fibers of passage which are altered differentially by gender and our experimental manipulations. In this paper, we report our findings when the original data are reanalyzed using a newly developed computer program. This program not only reproduced, with very high accuracy, the original means, but also permitted us to examine computer generated callosal width scores via a factor analysis procedure. Such a procedure yields useful information concerning the clustering of callosal fibers and thus contributes significantly to our hypothesis that discrete cortical regions are selectively sensitive to experimental variables. Factor analyses of the callosal variables and brain weight of 155 rats found 7 width factors, and an eighth factor which contained the variables of brain weight, callosal length, and callosal perimeter. Callosal area did not load significantly on any of these factors. The percentile locations of the width factors, starting at the anterior (genu) end were: widths 1-5, 6-17, 24-38, 46-57, 62-72, 79-95 and 96-99. Use of these factor scores in analyses of variance revealed that the male callosum is wider than the females, with the differences most pronounced in the genu and the most posterior portion of the splenium. Both age and early handling experience influenced the callosal width factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Callosal mediation of cortical inhibition in the lateralized rat brain

This paper tested a brain model for muricide. The model states that, in animals given handling stimulation in infancy, the right hemisphere is dominant for the occurrence of mouse killing and the left hemisphere acts to inhibit this behavior. On the assumption that the inhibition is mediated transcortically, it follows that severing the corpus callosum should result in an increase in muricide. This prediction was confirmed. In addition, prior research has found that animals not given extra stimulation in infancy show no evidence of lateralization for muricide. Therefore, splitting the brains of this group should not have any effect. This prediction was also confirmed. Latency analyses of muricidal rats found that those with only an intact right hemisphere killed much more quickly than those with only an intact left hemisphere. Sham controls had killing latencies similar to animals with only a right hemisphere. This pattern represents a brain model in which the right hemisphere is dominant for latency to kill. Rats exposed to mice in early life killed much more quickly than those without this early social experience, thus indicating that familiarity can reduce killing latency.

Characteristics of labeling of the cerebellar Purkinje neuron by L7 antiserum

Previously, it has been shown by light microscopy that antiserum to the L7 protein labels cerebellar Purkinje neurons. Herein we show by light and electron microscopic immunocytochemistry that all cerebellar Purkinje cells express L7 and that the gene product is distributed to all neuronal compartments, including the nucleus. Possible functional roles for L7, based on its subcellular localization, are discussed. L7 is proposed as an excellent marker molecule for future studies of normal and aberrant cerebellar development.

Alterations in the Dorsal Cochlear Nucleus of Cerebellar Mutant Mice

The idea that the dorsal cochlear nucleus (DCoN) contains a cerebellar-like microcircuit in its superficial layers was introduced several years ago (Lorente de No,’ 81; Osen and Mugnaini,’ 81). Support for this hypothesis comes from the fact that certain neuronal cell types residing in the superficial DCoN layers resemble those in the cerebellar cortex (Mugnaini et al.,’ 80a,b; Wouterlood et al.,’ 84; Wouterlood and Mugnaini,’ 84; Mugnaini,’ 85). Within this framework, our laboratory has been particularly interested in the so-called cartwheel neurons, originally termed globular or Type C cells by Lorente de No (’33,’ 79,’ 81). These neurons, with rounded cell bodies and extremely spiny dendrites that branch extensively in the molecular layer, are presumed to represent the equivalent of cerebellar Purkinje cells. The two cell populations derive from neighboring regions of the neuroepithelium at the rhombic lip, are generated during the same embryonic period (Miale and Sidman,’ 61; Altman and Das,’ 66; Taber-Pierce,’ 67; Martin and Rickets,’ 81; Willard and Martin,’ 86), and share several ultrastructural (Wouterlood and Mugnaini,’ 84) and neurochemical phenotypes (Mugnaini,’ 85; Mugnaini and Morgan,’ 87; Mugnaini et al.,’ 87; Saito et al.,’ 88; Mignery et al.,’ 89; Osen et al.,’ 90; and our unpublished observations using antisera to calbindin-28kD (Christakos et al.,’ 87), the cyclic GMP-dependent protein kinase (Lohmann et al.,’ 81), and the G-substrate (Schlichter et al.,’ 78) (see Table I). Additional evidence militating for a direct lineage relationship between cartwheel and Purkinje cells would be the demonstration that both cell types are equally affected by different genetic mutations mapping to single loci of diverse chromosomes.