Biomedical subjects

K Zilles

Publications and source records attributed to K Zilles.

At least 181 records · Page 10Linked to original sources

PubMed1995

Parcellation of the frontal cortex of the New World monkey Callithrix jacchus by eight neurotransmitter-binding sites.

The most extensive development during primate brain evolution involves the cortex of the frontal lobe, especially its prefrontal region. The distribution of neurotransmitter receptors is unknown in this part of the cortex of New World monkeys. The respective distributions of eight different receptors for the transmitters L-glutamate (L-glu and NMDA), gamma-amino-butyric acid (GABAA), noradrenaline (alpha 1), acetylcholine (M1 and M2) and serotonin (5-HT1 and 5-HT2) were therefore studied in cortical areas of the frontal lobe of the lissencephalic New World monkey, Callithrix jacchus. The results are compared to earlier data on Old World monkeys in order to obtain insight into evolutionary trends at the level of chemical neuroanatomy. Our results indicate that the density and laminar pattern of some receptors change precisely at the cytoarchitectonic boundaries between different cortical areas, while some other receptors do not exhibit measurable changes. For example, the premotor area 6 can be distinguished from prefrontal areas by its high concentration of adrenergic alpha 1 receptors as labelled with [3H] prazosin, with only the cingulate area 24 showing higher values. In other cases, the receptor distribution changes within a cytoarchitectonically homogeneous area. Thus, area 8 can be subdivided into dorsal and ventral regions on the basis of the distribution of GABAA, muscarinic and serotonin receptors. Comparison of these results in a New World monkey with receptor distributions in other primate species reveals much larger interspecies differences in the areas of the frontal lobe than e.g. in the primary visual cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Afferents to different layers of the dorsolateral isocortex in rats.

Fluorescent somatopetal tracers were used to infiltrate, by diffusion rather than injections, the dorsolateral cortex of one hemisphere in rats. In different animals the tracers penetrated into the cortex to different depths. We found several interesting features of the commissural system: first, there were no areas without commissural neurons. At least a few labelled cell bodies were present in a single-cell layer also in "acallosal" cortical areas. Secondly, there is a considerable variety of laminar distribution patterns of labelled perikarya in different areas. Thirdly, some cortical fields, which cytoarchitecturally appear uniform, can be subdivided according to different distributions of cell bodies with commissural projections. Fourthly, when only supragranular layers were infiltrated, labelled cell bodies were present mainly in the supragranular layers of the contralateral cortex. Infiltration of the first layer alone did not label any neurons in the contralateral cortex but did label neurons in layer VIb ipsilaterally. In the subcortex, the labelled perikarya were found in the structures already known to project directly to the cortex. In rats with the tracer restricted mainly to the supragranular layers, a conspicuously reduced labelling was found in the basal forebrain and the thalamus. In the thalami of those animals, labelled neurons were found only in paralamellar nuclei. The high sensitivity of the tracer used, together with infiltration of the entire dorsolateral cortex, allows us to conclude that probably all sources of innervation of the isocortex in rats have been seen.

Afferent Pathways↗

PubMed1995

Postnatal development of the human primary motor cortex: a quantitative cytoarchitectonic analysis.

The postnatal development of the human primary motor cortex (area 4) was analyzed in 54 individuals ranging in age from birth to 90 years. Three parameters defining major cytoarchitectonic features (areal fraction, numerical density and mean area of cells) were measured in vertical columns extending from the pial surface to the border between cortex and underlying white matter. The data were compiled in profile curves that reveal or more detailed laminar pattern than the classical cytoarchitectonic descriptions. The most pronounced decreases in numerical density and areal fraction of Nissl-stained cells profiles during early postnatal ontogeny are observed in layer II. A clearly delineable layer IV, which is still recognizable in the newborn, disappears gradually during the first postnatal months. Although the width of the cortex as a whole increases during this period, layer V, the main source of pyramidal tract fibers, is the only lamina that also increases in relative thickness. The other layers remain stable or become relatively thinner. These results reveal specific laminar growth processes in area 4, which take place in parallel with the functional maturation of the cortical motor system.

Adolescent↗

PubMed1995

Quantitative receptor autoradiography of eight different transmitter-binding sites in the hippocampus of the common marmoset, Callithrix jacchus.

The regional and laminar distributions of eight different transmitter-binding sites were measured in the marmoset hippocampus by means of quantitative in vitro receptor autoradiography. Receptors for 5-HT1, L-glutamate, N-methyl-D-aspartate (NMDA) and GABAA were similarly distributed. The highest concentrations of these receptors were found in the pyramidal layer of CA1 and the molecular layer of the dentate gyrus. The 5-HT2 receptors showed the highest concentrations in the oriens layer of CA2. The highest concentrations of muscarinic M1 receptors were seen in the pyramidal layer of CA1. Muscarinic M2 receptors were most densely concentrated in the pyramidal layers of CA1, CA2 and CA3. The noradrenergic alpha 1 receptors were most densely packed in the radiatum-lacunosum-molecular layer of CA2 and the molecular layer of the dentate gyrus. Statistically significant co-distributions of serotoninergic, glutamatergic and GABAergic receptors point to possible interactions between these receptor systems in the same hippocampal regions and layers. Comparisons of marmoset distribution patterns for GABAA, NMDA, L-glutamate and 5-HT1 receptors with those in human hippocampi and those of other primates showed similarities between them. Clear differences in the patterns of alpha 1, M1, M2 and 5-HT2 receptors could be seen between marmoset and human hippocampi, indicating a high degree of species specificity in a presumably "conservative" brain region. More similarities, however, could be found between marmoset and human hippocampi than between those of rat and human brains, especially in relation to 5-HT1 and GABAA receptors and L-glutamate-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Plasticity and neurotransmitter receptor changes in Alzheimer's disease and experimental cortical infarcts.

According to recently published data, the propagation of the typical neurofibrillary changes in Alzheimer's disease follows gradually and systematically the main pathways of fiber connections between different cortical areas. The functional deficits show a parallel development. Memory deficits as the first symptom of Alzheimer's disease can be explained by the initial lesion of the entorhinal-hippocampal connection. The next symptom is the impairment of emotional behaviour, which is caused by lesions in the hippocampus and the other parts of the limbic cortex. The following gnostic and praxic alterations can be explained by lesions in the association areas of the neocortex. Finally also motor disturbances become apparent, caused by lesions in the motor cortex. The tissue alterations in Alzheimer's disease represent a systemically spreading lesion in the cortex based on the destruction of synapses and finally of whole neurons, and on the impairment of normal neurotransmission. Since neurotransmission depends on transmitters and their receptors, the densities of transmitter receptors in the hippocampus, parietal association and premotor cortices in Alzheimer's disease were measured with quantitative receptor autoradiography. The degree of receptor changes in these regions decreases with the direction of the propagation of neurofibrillary changes from the hippocampus to the premotor cortex. With the exception of the GABAA receptor, the receptors in the hippocampus are reduced by approximately 70%. The reduction in the parietal association cortex amounts to only 30%. An upregulation of muscarinic M1 receptors was seen in the premotor cortex. The latter result is surprising in the context of a lesion model, but is in agreement with earlier immunohistochemical data about muscarinic receptors in the frontal cortex of Alzheimer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

PubMed1995

Areas of dormant glial fibrillary acidic protein (GFAP) immunoreactivity in the rat brain as revealed by automated image analysis of serial coronal sections.

Coronal vibratome sections of the rat brain were immunostained for glial fibrillary acidic protein (GFAP) a major cytoskeletal protein typical for astrocytes. Using computer-assisted image analysis of whole sections, a substantial heterogeneity in regional staining intensities was pointed out. The middle layers of the neocortex, the thalamus and caudate-putamen and the tectal and tegmental part of the mesencephalon were found to show no detectable staining, while peak staining intensities were measured for the pallidum, septal triangular nucleus, hippocampus, medial geniculate nucleus and interpeduncular nucleus. In some of the negative areas neural lesioning induced the appearance of GFAP immunoreaction parallel to an up-regulation of GFAP synthesis. On this basis it was assumed that GFAP immunoreactivity is dormant in these astrocytes and plastic changes in the neuropil trigger its expression.

Animals↗

PubMed1995

Is the length of the calcarine sulcus associated with the size of the human visual cortex? A morphometric study with magnetic resonance tomography.

PURPOSE: To determine whether the length and depth of the calcarine sulcus are associated and can be used for estimating the size of the primary visual area (area 17) and other regions in MR images of the human occipital lobe. METHODS: The length and depth of the calcarine sulcus and the projection areas of the mesial surface of the occipital lobe and of the total hemisphere were measured in MR images of 23 healthy subjects. RESULTS: A higher variability of the size of the projection area of the mesial surface of the occipital lobe compared with that of the remaining part of the hemisphere is found. The projection area of the mesial cortical surface of the occipital lobe is correlated with the length of the calcarine sulcus, but both parameters are not correlated with the depth of the calcarine sulcus and, therefore, also not with the size of the part of area 17 buried in the sulcus. CONCLUSION: The size of area 17 cannot be estimated by the length of the calcarine sulcus in MR images. Depth and length of the calcarine sulcus grow independently in the human brain. Different degrees of folding may cause the variability of architectonic areas.

Adolescent↗

PubMed1995

Mapping of human and macaque sensorimotor areas by integrating architectonic, transmitter receptor, MRI and PET data.

The human and macaque sensorimotor cortex was subdivided into numerous areas by a correlative analysis based on cytoarchitectonics, myeloarchitecture and the distribution of transmitter receptors. Receptor densities and laminar distribution patterns differ not only between motor and somatosensory regions, but also between different areas within these regions of the cortex. Changes in receptor distribution often match architectonically defined borders. Receptor findings provide new criteria for a more detailed mapping in the human brain which cannot be achieved by cytoarchitectonic analysis alone. Morphological data on these areas were integrated with functional data from positron emission tomography (PET) on the basis of a recently developed computerised brain atlas. The central sulcus marks the border between (1) the agranular motor cortex with a generally low density of glutamatergic, muscarinic, GABAergic and serotoninergic receptors, and (2) the granular somatosensory cortex with higher densities of these receptors. Rostral to the primary motor cortex, 2 isocortical areas are found on the mesial cortex which probably represent the functionally defined supplementary motor areas (SMA) SMA-proper (caudally) and pre-SMA (rostrally). Below SMA-proper the areas 24d (macaque) and the caudal cingulate motor area cmc (human) are located in the cingulate sulcus. Both regions correspond to the 'posterior cingulate motor areas' of recent PET studies and to the posterior part of the agranular cingulate cortex of architectonic studies. Below pre-SMA the area 24c (macaque) and the rostral cingulate motor area cmr (human) are located in the cingulate sulcus; they correspond to the 'anterior cingulate motor areas' of recent PET observations and to the anterior part of the agranular cingulate cortex of architectonic studies. Homologous sensorimotor areas can be defined in both species on the basis of common architectonic features.

Animals↗

PubMed1994

Electron microscopic demonstration of terminations of posterior thalamic axons on identified rubrospinal neurons in the rat.

In the rat, the major output of the posterior thalamic nucleus (PT) ends in the ventrolateral sector of the rostral two-thirds of the red nucleus. The aim of this study is to identify the rubral cells contacted by these thalamic efferents. In a first set of experiments, an anterograde neurotracer (PHA-L) was injected into the rostral part of the red nucleus. The only structure consistently and densely labeled was the contralateral spinal cord. Therefore, in a second set of experiments, massive HRP injections were made at different cervical levels in the spinal cord in combination with either electrolytic lesion or PHA-L injection in the contralateral PT. Both anterograde and retrograde labelings obtained in the RN were examined by correlated light and electron microscopy. Our findings indicate that anterogradely degenerated or labeled axons arising from the PT form synaptic contacts on HRP-filled dendritic processes of rubrospinal neurons. The thalamo-rubral articulation is direct and seems to be mainly axo-dendritic. These results support the possible participation of the PT in the modulatory control of spinal interneurons through the rubrospinal tract.

Animals↗

PubMed1994

Brain atlases--a new research tool.

Conventional brain atlases are collections of micrographs or schematic drawings of brain sections from one or a few brains in which anatomical structures are identified, for example, nuclei, cortical areas and fibre tracts. Conventional brain maps have now been replaced with modern computer-based brain atlases. The structures in computerized atlases are deformable so as to fit the sizes and shapes of individual brains, and transform three-dimensional reconstructions or images of brains into a standard brain format. In order to make generalizations about localization of function and structure at both the macroscopical and microscopical level computerized brain atlases are needed. Computerized brain atlases are also used to compensate for the shrinkage and distortions during sectioning and embedding of post-mortem brains, to study structural-functional relationships in the human brain at both the macroscopical and microscopical level, and variations in gross morphology and microstructure of the human brain, and for establishing a three-dimensional human-brain database for all of the above and also for topographically defined data from the literature.

Animals↗

PubMed1994

Aging of nucleolar organizer region in rat basal forebrain neurons related to learning and memory.

The nucleolar organizer of rat basal forebrain neurons was studied with histochemical and morphometrical techniques, in order to analyze quantitatively the morphological correlate of activity as it changes during learning and aging of the brain. The learning abilities of adult (2 months) and senile (30 months) rats were tested with a conditioned response learning paradigm. Four groups of rats were defined: one group consisted of untrained adults, a second group consisted of trained adults, and the senile rats were subdivided into one group, which was able to learn and another group which was not able to perform the test. Frozen sections through the basal nucleus were silver stained to visualize the nucleolar organizer and the area of its profile was measured. The data showed that the nucleolar organizer in both the trained adult and the senile rats who were able to learn, was much larger than that in the untrained adults and the senile rats who were not able to learn. In the latter groups the nucleolar organizers were of equal size. An additional finding was, that the senile rats who could not be trained, showed a lower neuronal density in the basal nucleus compared with that of the trainable senile and adult rats. The changes in the size of the nucleolar organizer are interpreted as a morphological sign of learning-induced increases in transcription and synthesis of ribosomal RNA.

Aging↗

PubMed1994

Volumetric comparison of hippocampal regions in 44 primate species.

Volumes of retrocommissural hippocampal regions (Subiculum, CA 1, CA 2, CA 3, hilus region, and fascia dentata) were measured using serial sections of 44 species of prosimian and simian brains, including man. The volumes were compared allometrically with those of the least encephalized eutherian mammals, the madagassian tenrecs (Insectivora, Tenrecinae; 4 species). The retrocommissural hippocampus is 2.9 times larger in prosimians, 2.4 times in non-human simians, and 4.1 times in man. The different hippocampal regions do not enlarge uniformly to the same degree as the total hippocampus. The regions can be grouped into three categories, according to the degrees to which they enlarge in primates: a) Structures with the greatest degree of enlargement are the subiculum and the field CA 1. b) An enlargement similar to that of the total retrocommissural hippocampus is seen for the hilus region. c) No or only a slight enlargement as compared to their sizes in tenrecs is observed for the hippocampal fields CA 2, CA 3, and the fascia dentata.

Animals↗

PubMed1993

Vasoactive intestinal polypeptide immunoreactive structures in the mouse barrel field.

Immunohistochemistry for vasoactive intestinal polypeptide was carried out in tangentially cut vibratome sections of the barrel cortex in adult mice. Sections through layer IV have revealed an association between the cytoarchitectonically visible modular organization of barrels and the distribution of immunoreactive axon terminals. These terminals are preferentially localized in the side region of a barrel, whereas the hollow shows a relative scarcity of these structures as shown with image analysis. This finding is the first direct demonstration of a modular distribution of vasoactive intestinal polypeptide-containing axon terminals in the neocortex.

Animals↗

PubMed1993

Long-term effects of anterograde degeneration on astroglial reaction in the rat geniculo-cortical system as revealed by computerized image analysis.

Changes in the expression of glial fibrillary acidic protein by astrocytes in the primary visual cortex of adult albino rats were analyzed with immunohistochemistry after unilateral destruction of the dorsal lateral geniculate nucleus. An increase in number of glial fibrillary acidic protein-immunoreactive astrocytes could be detected in the visual cortex of the side ipsilateral to the lesion in the short-term survival group (7-11 days post lesion), but this increase was extremely reduced after a postlesional survival time of 150 days. The quantitation of the glial response by image analysis showed, that the initial increase was mainly localized in the cortical layers II-IV, where the geniculo-cortical input terminates. The transient nature of this process was revealed by the measurements in the long-term survival group, where differences between experimental and control sides were substantially reduced. We conclude, that the remote glial response in the visual cortex is transient and that is disappearance indicates the end of a postlesional adaptation period in the neuropil.

Animals↗

PubMed1993

Layer V pyramidal cells in the adult human cingulate cortex. A quantitative Golgi-study.

The anterior and posterior parts of the human cingulate cortex differ in their absolute number of neurons per unit volume, with fewer neurons in the anterior part. To test the hypothesis that lower absolute number and packing density of neurons in the anterior cingulate cortex are associated with an increased complexity in the neuropil compartment, dendritic arborizations of layer V neurons in both cingulate parts were analyzed in a Golgi study. Results show that these neurons in the anterior cingulate cortex have more primary and secondary basal dendrites than those in the posterior cingulate cortex. This establishes an association of a higher complexity of the dendritic arborization in the anterior cingulate cortex with a lower cell number per unit volume and larger neuropil compartment. The significant lower degree of dendritic arborization in the posterior cingulate cortex is accompanied by a higher cell packing density. These structural differences are associated with functional differences between the two parts of the human cingulate cortex.

Adult↗

PubMed1993

Matching localization of vasoactive intestinal polypeptide (VIP) and VIP-receptor at pre- and postsynaptic sites in the mouse visual cortex.

Vibratome sections of the mouse occipital cortex were processed by double label immunohistochemistry to demonstrate the localization of the receptor for vasoactive intestinal polypeptide and the peptide itself. The receptor was found to be distributed in the cytoplasm and major dendrites of numerous cortical cells, mainly pyramidal neurons. Vasoactive intestinal polypeptide, on the other hand, occurred in a population of non-pyramidal neurons and axonal boutons. Image analysis revealed a close spatial association of peptide-containing presynaptic terminals with receptor-containing cells. Ultrastructurally, these connections represented symmetrical axo-somatic and axo-dendritic synapses. Our findings demonstrate a matching histological localization of vasoactive intestinal polypeptide and its receptor in the brain.

Animals↗

PubMed1993

Distribution of seven major neurotransmitter receptors in the striate cortex of the New World monkey Callithrix jacchus.

The distribution of seven different binding sites for the transmitters L-glutamate (L-glutamate binding sites and N-methyl-D-aspartate receptor), GABA (GABAA receptor), noradrenaline (alpha 1 receptor), acetylcholine (muscarinic M1 and M2 receptors) and serotonin (5-hydroxytryptamine1 receptor) are analysed in the primary visual cortex (area 17) of the common marmoset, Callithrix jacchus, using quantitative autoradiography. All binding sites show a well-defined laminar pattern, which changes sharply at the cytoarchitectonic border to area 18. The quantitative data show that the distribution of different receptors is relatively invariant across the cortical layers. Almost all receptors show a maximum in supragranular layers, low densities in layers IVA/IVB and a second maximum in layer IVC. Statistical analysis of these similarities in laminar distribution patterns of different receptors (co-distribution) reveals, as in other brain regions and species, that L-glutamate binding sites are co-distributed with N-methyl-D-aspartate, GABAA, and muscarinic M1 and M2 receptors. This may reflect the structural basis of a possible interaction between these receptors and their respective transmitters on the level of single cortical layers. Further co-distributions are found between N-methyl-D-aspartate, GABAA and M1, as well as between alpha 1 and M1 and finally between M1 and M2 receptors. Since not all receptors are co-distributed, the similarities in laminar patterns reveal specific aspects of the neurochemical organization of the cortex when receptors of different transmitter systems are analysed in the same brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Acetylcholinesterase activity and post-lesional plasticity in the hippocampus of young and aged rats.

Applying quantitative microscopic histochemistry, the activity of acetylcholinesterase was determined in the various layers of the rat hippocampus at three different levels along the rostrocaudal extent. Two age groups of animals were examined: young adults (two to three months old) and aged subjects (26 months old). Young adults were divided into controls, and animals killed eight and 35 days following bilateral ibotenate lesioning of the medial septum-diagonal band complex. Aged rats were divided into controls and animals 35 days post-lesion. Analysis of variance revealed that the mean acetylcholinesterase activities of the entire hippocampus of individuals were not significantly different between young and aged rats when averaged across controls and 35 days post-lesion. There was a significant decrease of acetylcholinesterase activity (-52%) in young adults eight days post-lesion as compared to controls, but a significant increase (+63%) took place until 35 days post-lesion as compared to eight days post-lesion. Significantly lower activities existed, however, in young (-22%) and aged rats (-18%) 35 days post-lesion as compared to controls. This decrease in mean activity was not age dependent. As acetylcholinesterase is considered to be a good cholinergic indicator in the hippocampus, the results suggest a homotypic collateral sprouting from spared cholinergic afferents following ibotenate lesion of the medial septum-diagonal band complex in young and aged rats. Based on the data obtained, it is reasonable to assume that there was no difference in the post-lesional plasticity of neuronal acetylcholinesterase between young adult and aged rats.

Acetylcholinesterase↗