Is the brain too complicated for simple replacement therapy?
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Animals↗
Biomedical subjects
I Divac
Publications and source records attributed to I Divac.
Bilateral thalamocortical projection in hedgehogs: evolutionary implications.
In adult hedgehogs with large unilateral cortical deposits of fluorescent somatopetal tracers, labelled perikarya were found not only in the ipsilateral but also contralateral thalamus. An exceptionally large number of contralaterally labelled neurons was seen in the ventrolateral nucleus, also at a considerable distance from the midline. Deposits of one of two different tracers in the frontoparietal cortex of each hemisphere appear to label different perikarya in each ventrolateral nucleus. This projection to the contralateral cortex in hedgehogs does not resemble thalamo-cortical connections in either adult or developing brains of other mammalian species. Among amniotes, only in pigeons have contralateral projections from the thalamus to the telencephalon been described. The somatosensorimotor system of hedgehogs may be the only known mammalian remnant of primitive vertebrate thalamocortical organization. Whether primitive or derived, the bilateral thalamocortical projection in hedgehogs shows that hedgehog brains cannot be uncritically taken to represent brains of primate ancestors.
Animals↗
Catecholamines and DOPAC in cortical and neostriatal regions during rats' learning of delayed alternation.
Dopamine, norepinephrine and DOPAC were measured in two cortical areas (the medial prefrontal and the posterolateral, Te2) and in the anterior and posterior neostriatum in rats which were exposed to three different experiences for three different lengths of time. One group learned delayed alternation and the two others served as controls. Throughout the training period all animals were housed in single cages. There was no significant effect of the kind of experience on any measure, but the length of exposure did affect some values: the amount of non-precursor dopamine was decreased significantly in both neostriatal samples. A significant increase of dopamine turnover and amount of norepinephrine was found in the Te2 area and in the posterior neostriatal sample. The observed changes are attributed to isolation stress. We conclude that although, as it has been described earlier, dopamine transmission is necessary for mediation of behavioural functions of the prefrontal system, it does not change quantitatively in the system during specific activity.
3,4-Dihydroxyphenylacetic Acid↗
Long-term retrograde labelling of neurons.
The intensity of labelling of neuronal perikarya with Fluoro-gold or rhodamine microspheres appeared unchanged in rats surviving one year after surgery. These tracers may be used for sequential labelling with long intervals and to study brain connections in precious specimens.
Animals↗
Cryostat sectioning of large brains made easy.
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Animals↗
Strain differences in catecholamine content of pigeon brains.
Concentrations of dopamine, noradrenaline and DOPAC were measured in 6 regions of telencephalon and in the cerebellar cortex of adult white Carneaux, and mixed breed pigeons of either sex. In both groups the regional differences in the amount of dopamine replicated the pattern we published earlier. The absolute values, however, differed in these groups: in all telencephalic regions the amount of dopamine was lower in the Carneaux strain than in the mixed breed specimens; in 4 of these regions the difference was statistically significant. A similar tendency was observed in the noradrenaline concentration but the difference was significant only in two telencephalic samples and the cerebellum. The concentration of DOPAC was significantly smaller in two telencephalic regions of the Carneaux pigeons.
Analysis of Variance↗
The N-CAM D2-protein as marker for synaptic remodelling in the red nucleus.
We have followed the time-course of changes in the concentration of 3 neuronal and one glial antigen in the red nucleus in rats after unilateral lesion of the cerebellorubral connections. The neuronal markers were the neuronal cell adhesion molecule (N-CAM) D2-protein which is prevalent in newly formed neuronal membranes, and the D1- and D3-proteins, which are found mainly in mature neuronal membranes. The glial marker was S-100, a cytoplasmic protein. Six days after the lesion no changes in the concentration of the markers were found in the partially deafferentiated red nucleus. However, 10 days after the lesion the D2-protein concentration was significantly increased, in contrast to the D1-protein concentration which was decreased. After a further 3 days the D2-protein concentration began to decrease, approaching the still significantly decreased D1-protein concentration. Twenty-one days after the lesion the marker protein concentrations were not significantly changed from normal. However, whereas the concentrations of neuronal membrane markers were lower, the glial S-100 concentration showed a tendency to increase. Furthermore, although the changes in D3-protein concentration were unable to reach statistical significance alone they always followed the direction of D1-protein and were significantly in variance with the changes in D2-protein and S-100 concentrations. Our results support the notion of the N-CAM D2-protein as a useful marker for synaptic turnover in adult brain.
Animals↗
Vertical ascending connections in the isocortex.
Different fluorescent tracers were applied to the surface of the cortex of rats, marmosets and one hedgehog. Irrespective of the kind of tracer and the depth of penetration, some perikarya of layer VI were labelled in each specimen and in all cortical regions. In the rat almost all labelled neurons were packed in sublayer VIb, in the marmoset such cells were dispersed throughout layer VI, whereas in the hedgehog the degree of their segregation to sublayer VIb was intermediate. Additional experiments in the rat indicated that most of the medium-sized neurons in the VIb layer project to layer I, that most of the perikarya projecting to the thalamus are localized in sublayer VIa, that different neurons project to the thalamus and to the surface of the cortex, and that only very few perikarya in deep parts of layers III and V and of sublayer VIa send axons or axon collaterals to layers I and II.
Animals↗
On the projections from the neostriatum to the cerebral cortex: the "displaced" neurons.
The entire dorsal and lateral cortex of one cerebral hemisphere of rats was infiltrated with different fluorescent tracers and the neostriatum was examined for labelled perikarya. In spite of the extensive infiltration of the cortex, such neurons were seen only sporadically in the ipsilateral neostriatum and almost only in the vicinity of the globus pallidus and the subcortical white matter. The size and shape of these neurons, and particularly their proximity to some cell groups which surround the neostriatum and project to the cerebral cortex, suggest that these neurons belong to the neighbouring structures such as the magnocellular nuclei of the basal forebrain, the claustrum and the VIb cortical layer.
Animals↗
Afferents of the frontal cortex in the echidna (Tachyglossus aculeatus). Indication of an outstandingly large prefrontal area.
Afferents of the large, electrically 'silent' frontal cortex in an egg-laying mammal, the echidna, were studied with the somatopetal axonal transport technique. This cortical area receives thalamic projections only from the anterior part of the anteromediodorsal region. The medial parts of the cortex receive afferents from more medial neurons, whereas the lateral area is innervated from the laterally placed perikarya of this thalamic region. The nonthalamic afferents to the frontal cortex are, with few exceptions, similar to the afferents of the prefrontal cortex in placental mammals. Cortical afferents originate in all layers of the contralateral symmetrical areas and in the ipsilateral paleocortex, especially the cortex in the bottom of the sulcus mu. The claustrum could not be identified, neither cytoarchitecturally nor hodologically. Pending confirmation from studies of the diencephalon, we presently conclude that the large anterior cortical area in this species corresponds to the prefrontal cortex of eutherian mammals. If this conclusion is correct, the echidna is the only species studied to date that has a proportionally larger prefrontal cortex than humans.
Animals↗
Efferent connections of the prefrontal cortex of echidna (Tachyglossus aculeatus).
In two echidnas injections of radioactively labeled amino acids were made into the cortical area which has been shown to receive afferents from the anteromediodorsal region of the thalamus and which is therefore tentatively identified as the prefrontal cortex. Efferents were found in the symmetrical area of the contralateral cortex, in the paleocortex and neostriatum bilaterally, the ipsilateral anteromediodorsal region of the thalamus, the hypothalamus, the ventral tegmental area, and the pons. No evidence was found of efferents caudal to the pons. The axons reached the contralateral side via the anterior commissure. The innervation of the cortex was columnar and that of the neostriatum patchy, as was previously demonstrated for comparable projections in placental mammals. The present material, albeit limited, shows some remarkable similarities between prefrontal efferents in the echidna and the placental mammals, including Old World monkeys.
Animals↗
Architectonics of the thalamus in the echidna (Tachyglossus aculeatus): search for the mediodorsal nucleus.
Architectural characteristics of the thalamus in echidnas and rats were compared in sections stained to reveal cell bodies, myelin, acetylcholinesterase, succinate dehydrogenase and cytochrome oxidase. Numerous species differences were noticed: in general, the thalamus is architecturally more homogeneous in echidnas than in rats, especially anteriorly. In this report we emphasize the presence of a relatively large structure localized in the anteromediodorsal part of the thalamus in echidnas. This structure, previously shown to project to the frontal cortex, contains very small amounts of acetylcholinesterase and the oxidative enzymes; in this respect it resembles the mediodorsal nucleus of rats. The same properties make this formation different from the anterodorsal and anteroventral nuclei in rats, the equivalents of which could not be identified in echidnas. The anteromediodorsal region of the thalamus in echidnas consists chiefly of two cytoarchitecturally different regions: the medial, 'polymorphic' part contains relatively small, densely packed, multiform perikarya, whereas the lateral, 'monomorphic' part is characterised by larger, sparse neurons with little cytoplasm and round, large, empty-looking nuclei in which the nucleolus is clearly seen. We conclude tentatively that this brain structure of echidnas corresponds to the mediodorsal nucleus in placental species. Further studies of connections and chemical properties will be essential to determine the degree of correspondence of the presumed 'frontal lobe system' in echidnas to that in other mammals.
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Neostriatal lesions impaired rats' delayed alternation performance in a T-maze but not in a two-key operant chamber.
Rats with lesions in the neostriatal region that belongs to the prefrontal system were trained in two versions of delayed alternation. They performed as proficiently as intact animals in a two-key operant chamber. The same operated rats took many more trials to reach criterion when subsequently compared with the same control group in a T-maze. This finding demonstrates that variants of delayed alternation are not equivalent for animals with lesions in the prefrontal system. Observations suggested that delayed alternation in the operant chamber may be mastered by positional mediation.
Animals↗
The prefrontal 'cortex' in the pigeon. Biochemical evidence.
Concentrations of dopamine and noradrenaline were determined in 6 regions of the telencephalon and in the cerebellum of the pigeon. Noradrenaline was rather evenly distributed. A significant variation was found of the dopamine-noradrenaline ratio (DA:NA), a measure which makes it possible to distinguish dopamine found in dopaminergic fibers from dopamine which is precursor of noradrenaline. The highest ratio was found in the anteroventromedial region (containing the presumed homologue of the mammalian neostriatum), and the next highest in the posteroventrolateral region (containing the archistriatum). Like in mammals, the lowest concentration of the non-precursor dopamine in the pigeon brain seems to be contained in the cerebellum. Among the regions which show physiological and anatomical similarities with the mammalian cerebral cortex, the DA:NA ratio was significantly higher in the posterodorsolateral, than in the posterodorsomedial and anterodorsomedial regions. The two dorsomedial regions contain the equivalents of the hippocampus and sensory cortical areas of mammals. The strong dopamine innervation of the posterodorsolateral region is comparable to that of the mammalian prefrontal cortex.
Animals↗
The prefrontal "cortex" in the pigeon catecholamine histofluorescence.
The prefrontal cortex of mammals is densely innervated with dopaminergic fibers. We report a comparable, dense network of catecholamine (probably dopamine)-containing fluorescent fibers in the posterodorsolateral neostriatum of the pigeon. This region is clearly separable from paleostriatum augmentatum, lobus parolfactorius, posterior archistriatum, posteromedial corticoid and septum, all of which also show strong catecholamine fluorescence. Parallel biochemical, anatomical and neurobehavioral data support the suggestion that posterodorsolateral neostriatum in the pigeon may be comparable to the mammalian prefrontal cortex. Thus the telencephalic tissue represented as the prefrontal cortex in mammals and the posterodorsolateral neostriatum in the pigeon, may turn out to be a phylogenetically ancient neural device.
Animals↗
Focal cortical seizures prevent HRP and HRP-WGA labeling only in neurons bidirectionally connected to the cortex.
Intracortical implants of polyacrylamide gel containing horseradish peroxidase labeled cortical efferents and perikarya in some cortical areas and a number of subcortical formations. When epileptogenic penicillin was added to the gel, no labeling was seen in the efferents and cell bodies of the cortex, thalamus, or claustrum, whereas the magnocellular nuclei of the basal forebrain, raphe nuclei and locus coeruleus did contain the label.
Animals↗
The monocular and binocular subfields of the rat's primary visual cortex: a quantitative morphological approach.
Primary visual cortex in the rat was studied by a variety of methods: transsynaptic transport of labelled amino acids, 2-deoxyglucose, and staining for perikarya, myelin, and acetylcholinesterase. The analysis was aided by a computer-controlled television image analyzer. The results obtained with different methods agree with one another in describing the position and extent of the entire primary visual cortex as well as its monocular (medial) and binocular (lateral) subareas.
Acetylcholinesterase↗
Catecholamine microfluorometry of nigral perikarya and tyrosine hydroxylase assay in some telencephalic structures of rats exposed to different behavioral situations.
In an earlier attempt to detect biochemical changes in the prefrontal system of rats performing a task sensitive to prefrontal damage, significant changes in amount of synaptic proteins were found only in the prefrontal cortex and only in the yoked control group. In a similar experimental paradigm, we measured presently activity of tyrosine hydroxylase in several telencephalic formations and intensity of dopamine fluorescence in neurons of the substantia nigra. The neurons in the medial and anterior portion of the substantia nigra of all experimental groups fluoresced significantly stronger than those in the lateral and posterior portions. The activity of tyrosine hydroxylase was 3-4 times higher in the medial prefrontal area than in the occipital cortex. No significant behavior-induced changes were detected in either of these variables. These results-in turn (1) demonstrate an unexpectedly strong dopamine concentration in the nigral neurons which innervate the prefrontal target of the neostriatum; (2) support the evidence of a strong dopaminergic innervation of the prefrontal cortex; and (3) indicate that the dopaminergic transmission in the prefrontal system was not affected by presumed activation of the system to a degree detectable by the presently used methods.
Animals↗