Biomedical subjects

A Kalsbeek

Publications and source records attributed to A Kalsbeek.

60 records · Page 4Linked to original sources

PubMed1989

Morphometric analysis of prefrontal cortical development following neonatal lesioning of the dopaminergic mesocortical projection.

In this study the possibility that dopamine (DA) plays a trophic role in cortical development was studied by analysing cortical morphology and dendritic arborization of pyramidal cells after neonatal depletion of DA. The prefrontal cortex (PFC) was depleted of a DA innervation from postnatal day 1 onwards by thermal lesions of the DA cell group (A10) in the ventral tegmental area. Measurements of the cortical thickness and volume of the PFC subareas did not reveal any gross alterations. The DA-depleted animals, however, showed a 30% decrease in the total length of the basal dendrites of the pyramidal cells in layer V of the medial PFC. These cells constitute the primary target of the dopaminergic innervation in the prefrontal cortex. The decreased dendritic length was due mainly to a reduced branching frequency of the basal dendrites. The present results of the dendritic measurements support a trophic role for DA in neuronal differentiation.

Aging↗

PubMed1989

Influence of the mesocortical dopaminergic system on activity, food hoarding, social-agonistic behavior, and spatial delayed alternation in male rats.

In order to assess the behavioral role of the dopaminergic mesocortical input to the prefrontal cortex, bilateral lesions were made in the ventral tegmental area (VTA). The possibility of a functional recovery by the administration of a dopamine agonist was examined. General activity, food hoarding, social-agonistic behavior, and spatial delayed alternation performance were recorded in rats with VTA lesions and in sham-operated animals. In the open field animals with VTA lesions were more active but showed less anxiety. Food hoarding was impaired. In dyadic interactions with sham-operated opponents, VTA rats were socially more active, whereas sham operates performed more keeping down and aggressive grooming. This behavioral deficit was partially recovered when apomorphine was administered prior to testing. VTA animals were impaired in the performance of a spatial delayed alternation task with an intertrial interval of 15 s, whereas no impairment was found with a 0-s intertrial interval. The theoretical implications of these findings are discussed.

Aggression↗

PubMed1988

Neonatal thermal lesions of the mesolimbocortical dopaminergic projection decrease food-hoarding behavior.

In order to examine the effect of neonatal depletion of the dopaminergic mesocortical projection on the development of prefrontal cortex-mediated behaviors, male and female adult rats with neonatally applied thermal lesions of the dopaminergic A10 cell group in the ventral tegmental area were studied in a food-hoarding situation. Control male animals hoarded significantly more pellets than females. Neonatal depletion of dopamine in the prefrontal cortex strongly decreased food-hoarding activity in contrast with previous studies by others which have shown that neonatal lesions of the prefrontal cortex allow sparing of food-hoarding activity. Biochemical analysis demonstrated an approximately 50% depletion of both dopamine and serotonin in the prefrontal cortex of males, whereas noradrenaline levels were unchanged. The brains of the female rats were used to visualize the decreased dopaminergic and serotonergic innervation of the forebrain. Hoarding scores showed a significant positive correlation with the measured dopamine content of the medial prefrontal cortex, and not with the serotonin content. These results imply that the integrity of the dopaminergic projection to the prefrontal cortex is essential for food-hoarding behavior to occur and that food-hoarding activity is not spared after neonatal depletion of dopamine.

Animals↗

PubMed1988

Development of the dopaminergic innervation in the prefrontal cortex of the rat.

The pre- and postnatal development of the dopaminergic innervation in the prefrontal cortex (PFC) of the rat is described from embryonic day 14 through postnatal day 90. By embryonic day 15 the dopamine (DA)-containing fibers reach the anlage of the lateral neocortex; 2 days later the first fibers have reached the subplate of the future prefrontal cortex. The process of entering the cortical plate starts just before birth. Prenatally, some dopaminergic fibers can be observed in the marginal zone of both the lateral and the medial wall of the hemisphere. Within 48 hours after birth a large number of dopaminergic fibers can be observed in the marginal zone, i.e., the future layer I, in some subareas of the PFC. A transient appearance of DA-positive fibers is noticed in the late embryonic and early postnatal periods especially in the marginal zone and possibly in the superficial layers of the pregenual cingulate cortex. Changes in the morphology of DA fibers at P4 suggest that the actual DA innervation starts at this age. From postnatal day 6 the different subareas of the PFC can be recognized according to the characteristics of the topographical distribution of the dopaminergic fibers. Until postnatal day 60 the density of the dopaminergic fibers continues to increase. No difference in density and topography was observed between postnatal days 60 and 90.

Aging↗

PubMed1988

The pre- and postnatal development of the dopaminergic cell groups in the ventral mesencephalon and the dopaminergic innervation of the striatum of the rat.

In the adult rat the striatum is a compartmentalized structure, which is reflected in the inhomogeneous distribution of dopamine. As a first step to test the hypothesis that dopamine plays an organizational role in the development of the striatum, the ontogeny of the dopaminergic system was studied in detail with immunocytochemical methods employing antibodies against dopamine. Rat embryos, fetuses, pups and adults were perfusion-fixed with glutaraldehyde on all prenatal days from E11 onward, postnatally on P2, P4, P6, P7, P8, P13, P14, P20, P21, and in adult age. On E13 the first dopaminergic cells are detected in the ventral prosencephalon. On E14 two dopaminergic cell groups are present in the ventral mesencephalon, and fibres of these cells reach the ventrolateral part of the ganglionic eminence. In the next two days both the cell groups and their projections rapidly increase in size. On E17 the afferent dopaminergic fibres to the striatum become aligned and form huge bundles that are closely associated with the fascicles of the internal capsule. Rostrally, the development of the striatal dopaminergic innervation shows a clear ventrolateral to dorsomedial gradient, whereas more caudally the dopaminergic fibres innervate the striatum from a ventromedial position. The lateral parts of the otherwise compact mesencephalic cell groups consist of loosely arranged cells. From E17 onward these cells become arranged into a dorsal and a ventral group. Just before birth, on E21, the primordia of the dopaminergic cell groups in the substantia nigra pars compacta and pars reticulata can be observed. On E19 several centres with extensive fibre ramifications along the dorsolateral margin of the caudate putamen represent the first signs of the inhomogeneous distribution of dopaminergic fibres in the dorsal striatum seen during the next two weeks. In the following pre- and postnatal days these so-called dopaminergic "patches" also appear more medially. By the third postnatal week most of the patches are no longer detectable, and only the most dorsolaterally located ones, i.e. in the region where they first were detected on E19, remain visible through to the adult stage. Prenatally, no varicosities can be observed in the dopaminergic fibres. The first varicosities appear after birth. Their number increase rapidly during the first and second postnatal weeks and reaches near adult levels on P20. The development of the striatal dopaminergic innervation, and that of the "patches" in particular, is discussed in relation to the development of the mesencephalic dopaminergic cell groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1987

Effects of neonatal thermal lesioning of the mesocortical dopaminergic projection on the development of the rat prefrontal cortex.

The role of dopamine (DA) in the development of the prefrontal cortex (PFC) was investigated by depleting the dopaminergic innervation of the PFC. A new stereotaxic procedure made it possible to produce small lesions in 1-day-old rats confined to the A10 group of dopaminergic cell bodies in the ventral tegmentum, from which the dopaminergic projection to the PFC originates. The variety in the lesions revealed a clear topographical organization of the efferent connections of the ventral tegmental area (VTA) to the prefrontal cortex. As far as we know from the literature the data presented in this study are a first direct indication of a neurotrophic role for dopamine in the development of the prefrontal cortex. When the prefrontal cortex was depleted of the dopaminergic innervation from birth on, by lesioning the cells of origin on postnatal day 1, the cortical thickness in the medial PFC was reduced by about 6%. Although coagulative lesions in the ventral tegmentum cause also a depletion of cortical serotonin, cortical reduction seems to be rather the result of the absence of dopamine during its development. This is indicated by the absence of a significant cortical thickness reduction in the dysgranular part of the first somatosensory cortex, which receives a serotonergic but no dopaminergic innervation.

Animals↗