Functional neuroanatomy of the prefrontal cortex: autonomic interactions.
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Biomedical subjects
Publications and source records attributed to C G Van Eden.
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The expression of the nuclear protein p53 in oligodendrogliomas was investigated by immunohistochemistry, using a monoclonal anti-p53 antibody (DO-7) on formalin-fixed, paraffin-embedded material in 84 histologically verified cases, and compared with the histopathological grade and survival. p53-immunoreactive cells were found in 75 per cent of the samples acquired at the first biopsy. The p53 labelling index was not related to the degree of nuclear anaplasia. Tumour cases with more than 75 per cent p53 immunostained cells had a rapidly fatal clinical course. However, no significant correlation was found between p53 labelling index and tumour grade, mitotic index, or ploidy status. In most tumour recurrences (n = 25), the p53 labelling index increased or remained at the level of the first biopsy. In five cases (6 per cent), p53 was absent in the first sample as well as in the recurrence. Irrespective of the underlying aberration of either the gene or the metabolic pathway of p53, it is concluded that a high percentage (i.e., more than 75 per cent) of p53-immunolabelled cells is predictive of an unfavourable clinical course, while a percentage lower than 75 per cent immunoreactive cells does not exclude a rapid fatal outcome.
This study examines whether treatment with GM1 ganglioside or the corticotropin (ACTH)(4-9) analogue ORG2766 can facilitate the behavioural recovery of adult rats with medial prefrontal cortex (mPFC) lesions, as animals are impaired in their food hoarding and spatial delayed alternation performance following mPFC lesions. No ameliorating effects of GM1 treatment on performance of these behaviours were observed. Although treatment with ORG2766 somewhat improved the hoarding performance of lesioned animals, the intermediate amount of pellets hoarded was not significantly different from that of either sham-operated or vehicle-treated lesioned rats. No effect of ORG2766 treatment was observed in the spatial delayed alternation test. Further, no changes were detected in the mesocortical dopamine innervation, presumed to be involved in the neural mechanism of behavioural sparing, in response to either treatment.
A multivariate analysis of spontaneous single neuron firing in the developing prefrontal cortex (PFC) of urethane anesthetized rats has been made using selected spike-train parameters. In particular, the development of modal interspike intervals closely paralleled the volumetric 'overshoot' reported earlier by us for rat PFC. Thus, the growth phase is characterized by progressively higher firing rates associated with longer modal intervals (i.e., a change from phasic to tonic firing, suggestive of increasingly effective inhibition). In contrast, the subsequent abrupt reduction in PFC volume is accompanied by the appearance of extremely short interspike intervals with no concomitant change in overall mean discharge rates ('burst' firing). This last development could be largely due to the 'pruning' of excessive excitatory synaptic contacts.
In oligodendroglial tumors the intermediate filament glial fibrillary acidic protein (GFAP) may be expressed by cells with the morphologic characteristics of typical oligodendrocytes (gliofibrillary oligodendrocytes [GFOC]) and by miniature forms of gemistocytes (minigemistocytes) as well. These latter cell types have been regarded as transitional cells that represent intermediate forms between an oligodendroglial and an astrocytic phenotype. Furthermore, in oligodendrogliomas GFAP may be expressed by intermingled classic large gemistocytes, which are not considered transitional cells. In a retrospective study of 111 oligodendrogliomas, the presence of the various GFAP-positive cell types was correlated with the survival rates of the patients. Therefore, GFAP expression was visualized with the use of an indirect conjugated peroxidase method. The survival times of the patients were recorded and statistical comparisons were made. The percentage of GFAP-positive tumor cells is increased in oligodendrogliomas of 28 patients who underwent a second biopsy (all these patients had been treated with radiation therapy as well). It was found that neither the presence of GFOC nor that of minigemistocytes is predictive of the survival. In contrast, patients with classic gemistocytes had survival lengths approximately twice as short as those of patients who did not have these cells in their tumors. No clear correlation was found between tumor grading or any of the individual histopathologic features with the presence of the various GFAP-positive cell types. The ominous sign of the presence of gemistocytes in oligodendrogliomas confirms some earlier reports about the prognostic significance of this cell type in astrocytomas.
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The present study shows that in the prenatal rat neocortex the GABA immunoreactive neurons are not limited to the marginal, subplate, and intermediate zones, but are also found in all fetal zones of the cerebral anlage. The first GABA-ergic cells are observed on embryonic day 14 in the plexiform primordium. On embryonic day 15, a second population of GABA-ergic cells is observed in the intermediate zone. Beginning on day 16 of gestation and continuing throughout gestation, GABA-ergic neurons are observed in the marginal zone, the subplate zone, the cortical plate, and the ventricular and subventricular zones. Furthermore, while the number of GABA-ergic cells in the cortical plate increases, GABA-ergic neurons in the intermediate zone and subventricular zone decrease in number after embryonic day 19.
The neuronal cell types and their morphology in the nucleus basalis (NB), in the horizontal and vertical limbs of the diagonal band of Broca (NHL and NVL), and in the medial septal nucleus (MSN) were examined in Golgi-impregnated material. Cells appeared as multipolar or oligopolar and displayed a variable dendritic morphology; their somata varied considerably both in shape and size. The dendrites of most cells were restricted within nuclear boundaries, although occasionally neurons located near boundaries, particularly cells in NHL, extended dendritic arbors into neighboring areas. Axons were rarely seen, but when they were found they were generally not impregnated beyond the initial segment and displayed no apparent preferential direction. Three types of cells common to each of the 4 nuclear groups could be identified on the basis of soma shape and dendritic form. The first type included large multipolar neurons with triangular or polygonal perikarya and typically 3-5 dendrites emerging from the poles of each cell. These cells were especially numerous in NB, NHL, and NVL, but were much less frequent in MSN. The second type comprised medium-sized cells with round or oval somata and a small number, usually 2-3, of dendrites. They constituted a large percentage of the cell population in MSN, but were also encountered in NHL and NVL as well as in NB. The third type consisted of cells with fusiform or spindle-shaped somata with usually single dendrites emanating from each pole of the cell. A rare but distinct type of spindle-shaped neuron with dendrites bearing a rich complement of long and thin appendages was observed mainly in the ventral border of NHL. The present observations suggest that although the proportions and sizes of the 3 types of neurons vary between the 4 nuclei, neurons throughout the basal forebrain share common morphological characteristics.
Golgi-Stensaas and rapid-Golgi staining techniques are used to study neuronal differentiation in the developing human prefrontal cortex in fetuses, premature infants, and full-term newborns from 10.5 to 40 weeks of gestation. Horizontal neurons (Cajal-Retzius neurons) above the cortical plate (in the marginal zone) and randomly oriented neurons below the cortical plate (in the primordial subplate) are more differentiated than the immature bipolar cortical plate neurons in the 10.5-week fetus. During 13.5-15 weeks of gestation the fetal subplate zone can be clearly distinguished-between the cortical plate and the intermediate zone. This subplate zone contains more mature neurons than the cortical plate, especially polymorphous neurons. The basic features of the apical and basal dendrites of pyramidal neurons develop between 17 and 25 weeks of gestation, before the thalamocortical fibres invade the cortical plate. Intensive differentiation of the subplate neurons occurs in this period, when various types of afferent fibres reside in the subplate zone. At least five neuronal types can be distinguished in the subplate, i.e., polymorphous, fusiform, multipolar, normal, and inverted pyramidal neurons. The ingrowth of afferent fibres into the cortical plate between 26 and 34 weeks of gestation coincides with intensive dendritic differentiation and the appearance of spines on dendrites of the prospective layer III and V pyramidal neurons as well as with the differentiation of the double bouquet interneurons in the prospective supragranular layers and layer IV. Multipolar nonpyramidal neurons with the dendritic features of basket neurons are observed between 32 and 34 weeks of gestation in future layer V. They are less differentiated than the double bouquet neurons. The neurons of the subplate zone continue their dendritic differentiation after 26/27 weeks of gestation and are still observed in the full-term newborn. The axonal pattern of the subplate neurons suggests a possible functional role for them as either interneurons or projection neurons.
Although early depletion of noradrenaline is known to affect the morphological development of various structures in the brain, it is not clear what implications this has for adult behaviour. In the present study, 6-hydroxydopamine (6OHDA) was injected into the lateral ventricles of 12 day old rats, permanently destroying most of the noradrenergic innervation of the spinal cord and of all the brain areas examined except for the pons/medulla, and reducing the dopamine content of the cerebral cortex considerably. The noradrenaline content of the heart, as well as general developmental parameters such as food intake and body weight, were unaffected. Despite the extensive noradrenaline depletion during development, these rats' spatial memory--as determined in a radial maze task--was no worse than that of controls. In a lever-pressing task the 6OHDA treated rats made no more errors than did controls, but performed more slowly. The results indicate that at least some aspects of learning, memory and sensory-motor ability can develop normally when the noradrenergic innervation of the brain is largely destroyed.
In the present study the dopaminergic innervation of the prefrontal cortex was studied by means of a recently developed anti-dopamine serum. This method can demonstrate endogenous dopamine in a specific way, and offers the opportunity to study the distribution of dopaminergic fibres in the cortex in detail in counterstained sections. Furthermore, dopaminergic nerve endings can be visualized at the electron microscopic level. Light microscopic observations demonstrated that the highest density of dopaminergic fibres in the frontal cortex is found in the prefrontal cortex and the infralimbic cortex. Within the prefrontal cortex, a good correlation is found between regional differences in distribution of dopaminergic fibres and the cytoarchitectonic parcellation of this part of the cortex. Outside the prefrontal cortex dopaminergic fibres were observed in adjacent frontal areas, the cortex surrounding the entire rhinal sulcus and the retrosplenial cortex. Electron microscopic observations demonstrated dopaminergic terminals through all cortical layers. The majority of dopaminergic terminals in the prefrontal cortex from synaptic contacts with dendritic processes. The synaptic profiles were usually symmetric and were characterized by the presence of many clear vesicles and an occasional dense-core vesicle.
The postnatal ingrowth of thalamocortical fibers from the mediodorsal nucleus to the prefrontal cortex was investigated in relation to the development of cortical lamination. Like the dopaminergic fibers in the prefrontal cortex and the thalamic fibers in the visual cortex, the mediodorsal fibers have entered the prefrontal cortex at birth. Most of the fibers are found in the developing layer VI, but, in contrast to the above-mentioned systems, a considerable number of mediodorsal fibers have already penetrated into the upper, most immature part of the cortical plate on postnatal day 1. From day 1 to day 7 an increasing number of mediodorsal fibers reach the upper cortical plate, which by then is developing layer III, the terminal layer of these fibers. The reciprocal connection from the layer VI cells of the prefrontal cortex to the mediodorsal nucleus develops between day 4 and day 9. Finally, the projection from the contralateral prefrontal cortex to the mediodorsal nucleus is established around day 10. The early presence of the mediodorsal fibers in the upper, differentiating cortical plate might indicate an important role for the mediodorsal fibers in the laminar development of the prefrontal cortex.
Wistar rats of the inbred CPB-WE and the random bred Cpb:WU strains have been used in neuroanatomical studies. In both groups of rats a high incidence of hydrocephalus was observed. In the CPB-WE rats the ventricular dilatation was accompanied by optic tract lesions and microphthalmia. The present report describes the gross and microscopic findings in these rats and discusses the possible aetiology.
This paper gives an account of the cytoarchitectonic characteristics that make it possible to delineate, from as early as day 6, different subareas of the prefrontal cortex of the rat. Three phases can be distinguished during postnatal development. The first phase (from day 1 until day 18) is dominated by differentiation of the neurons within the cortical plate and by the formation of the cortical layers. At day 1, regional differences are observed in the cytoarchitecture of the cortical plate which correspond to the future subareas of the prefrontal cortex. The formation of layer IV occurs in the dorsolateral cortex around day 6, and from this age the agranular prefrontal cortex is well demarcated from the other parts of the frontal cortex. Between day 6 and day 10, the cortical plate has disappeared and all cortical layers can be recognized in the prefrontal cortex. Differentiation of the cells within the cortical layers changes the cytoarchitectonic character of the layers through day 18. During the second phase (from day 18 until day 30) little change occurs in the cytoarchitectonic characteristics of the prefrontal subareas. During the third phase (from day 30 until day 90) the delineation of the cortical layers becomes less clear in Nissl-stained sections, and the individual cytoarchitectonic variance increases. On the basis of cytoarchitectonic criteria it can be concluded that the orbital prefrontal cortex develops earlier than does the medial prefrontal cortex.
The medial and orbital parts of the prefrontal cortex (PFC) increase in volume during the first weeks of postnatal life. At the end of this period, however, the volumes of both parts of the PFC reach a significantly higher value than in adulthood. Subsequently the volumes decrease until the adult volume is attained. The three subareas of the medial PFC (i.e., the medial precentral area, the dorsal anterior cingulate, and the prelimbic area) reach a maximum volume around day 24, while the two orbital PFC subareas (i.e., the dorsal and ventral agranular insular areas) attain their maximum value around day 30. The differences found in the growth pattern of the five PFC subareas, which are innervated by specific subnuclei of the mediodorsal nucleus of the thalamus, suggest a role of these subnuclei in the PFC development.
Left over right asymmetries in volume have been found in two subareas of the medial prefrontal cortex (PFC), and a right over left in the orbital PFC. The asymmetries change during development, indicating differential growth rates for left and right PFC parts. The asymmetry of the medial PFC reached significance from day 10 until day 18 and at day 90. The asymmetry of the orbital PFC reached significance from day 30 until day 60. At day 90 no significant asymmetry is demonstrated in this part of the PFC. A significant sexual dimorphism was demonstrated for the dorsal agranular insular subarea (AId) in the orbital PFC.
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