Complex patterns and simple architects: molecular guidance cues for developing axonal pathways in the telencephalon.
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Animals↗
Biomedical subjects
I Kostović
Publications and source records attributed to I Kostović.
Nitrinergic neurons in the developing and adult human telencephalon: transient and permanent patterns of expression in comparison to other mammals.
A subpopulation of cerebral cortical neurons constitutively express nitric oxide synthase (NOS) and, upon demand, produce a novel messenger molecule nitric oxide (NO) with a variety of proposed roles in the developing, adult, and diseased brain. With respect to the intensity of their histochemical (NADPH-diaphorase histochemistry) and immunocytochemical (nNOS and eNOS immunocytochemistry) staining, these nitrinergic neurons are generally divided in type I and type II cells. Type I cells are usually large, intensely stained interneurons, scattered throughout all cortical layers; they frequently co-express GABA, neuropeptide Y, and somatostatin, but rarely contain calcium-binding proteins. Type II cells are small and lightly to moderately stained, about 20-fold more numerous than type I cells, located exclusively in supragranular layers, and found almost exclusively in the primate and human brain. In the developing cerebral cortex, nitrinergic neurons are among the earliest differentiating neurons, mostly because the dominant population of prenatal nitrinergic neurons are specific fetal subplate and Cajal-Retzius cells, which are the earliest generated neurons of the cortical anlage. However, at least in the human brain, a subpopulation of principal (pyramidal) cortical neurons transiently express NOS proteins in a regionally specific manner. In fact, transient overexpression of NOS-activity is a well-documented phenomenon in the developing mammalian cerebral cortex, suggesting that nitric oxide plays a significant role in the establishment and refinement of the cortical synaptic circuitry. Nitrinergic neurons are also present in human fetal basal forebrain and basal ganglia from 15 weeks of gestation onwards, thus being among the first chemically differentiated neurons within these brain regions. Finally, a subpopulation of human dorsal pallidal neurons transiently express NADPH-diaphorase activity during midgestation.
Animals↗
Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area.
The small magnocellular group located within the rostrolateral extension of the basal forebrain was named and described as the nucleus subputaminalis in the human and chimpanzee brain by Ayala. Analysis of cytoarchitectonic and cytochemical characteristics of this cell group has been largely disregarded in both classical and more current studies. We examined the nucleus subputaminalis in 33 neurologically normal subjects (ranging from 15 weeks of gestation to 71 years-of-age) by using Nissl staining, choline acetyltransferase immunohistochemistry, acetyl cholinesterase histochemistry and nerve growth factor receptor immunocytochemistry. In addition, we applied reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and calbindin-D28k immunocytochemistry in three neurologically normal subjects. At the most rostrolateral levels we describe the previously poorly characterized component of the lateral (periputaminal) subdivision of the subputaminal nucleus, which may be human specific since it is not described in non-human primates. Moreover, we find the human subputaminal nucleus best developed at the anterointermediate level, which is the part of the basal nucleus that is usually much smaller or missing in monkeys. The location of subputaminal cholinergic neurons within the frontal lobe, the ascension of their fibers through the external capsule towards the inferior frontal gyrus, the larger size of the subputaminal nucleus on the left side at the most rostral and anterointermediate levels and the most protracted development among all magnocellular aggregations within the basal forebrain strongly suggest that they may be connected with the cortical speech area. These findings give rise to many hypotheses about the possible role of the subputaminal nucleus in various neurodegenerative, neurological and psychiatric disorders, particularly Alzheimer's disease and primary progressive aphasia. Therefore, future studies on the basal forebrain should more carefully investigate this part of the basal nucleus.
Adolescent↗
C-pathway polysialogangliosides are transiently expressed in the human cerebrum during fetal development.
Gangliosides are assumed to play a crucial role in processes of cellular recognition and interaction important for neural development. They are designated as cytochemical markers of neuronal maturation, as striking changes in the ganglioside pattern parallel the nervous system development. Of particular interest to us are numerous studies that reported during migration of postmitotic neurons and axon formation in developing avian and mammalian brains a transient accumulation of highly sialylated c-pathway gangliosides. However, it has thus far been thought that c-pathway gangliosides do not appear in the human cerebrum; their absence could be somehow interpreted in the light of an evolutionary trend in the pattern of brain gangliosides: by increasing the phylogenetic scale this pattern changes by an accretion of less sialylated gangliosides and switches from c- via b- to a-series, respectively. The present study presents both biochemical and immunocytochemical evidence for the existence of c-pathway gangliosides in the human cerebrum during prenatal life, and their localization in discrete neuronal populations and growing axonal pathways.
Aging↗
Transient fetal structure, the gangliothalamic body, connects telencephalic germinal zone with all thalamic regions in the developing human brain.
Previous studies reported that telencephalic proliferative zones contribute to the development of the pulvinar thalamic nucleus in the human brain (Rakic and Sidman [1969] Z. Anat. Entwicklungsgesch. 129:53-82). The present study examined their possible contribution to the development of other thalamic nuclei. Postmortem brain tissue from human fetuses ranging between 10.5 and 40 weeks of gestation (wg) was processed by Nissl staining, Golgi impregnation, and MAP2 (microtubule-associated protein 2) immunocytochemistry. The gangliothalamic body, suggested to serve as a conduit for cells migrating from the ganglionic eminence to the thalamus, was found in the period from 15 to 34 wg in all rostrocaudal thalamic regions, particularly at the level of the anterior nuclear complex, mediodorsal and pulvinar nucleus, and in addition, the lateral geniculate nucleus. In Nissl-stained sections, the gangliothalamic body is a thin cellular layer situated beneath the thalamic surface, near the telencephalo-diencephalic junction. In Golgi- and MAP2-stained sections, it is a stream of mostly bipolar cells extending from the ganglionic eminence to the medial thalamus. In addition, MAP2-immunoreactivity confirms the neuronal nature of its cells. The present study further supports the hypothesis that certain neurons migrate from the ganglionic eminence to the thalamus through the transient gangliothalamic body during fetal development. Moreover, our data indicate that both the association (mediodorsal and pulvinar), as well as the anterior (limbic) and specific relay nuclei are potential recipients of the telencephalic neurons.
Embryonic and Fetal Development↗
Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease.
In order to observe changes owing to aging and Alzheimer's disease (AD) in the volumes of subdivisions of the hippocampus and the number of neurons of the hippocampal formation, 18 normal brains from subjects who died of nonneurological causes and had no history of long-term illness or dementia (ten of these brains comprised the aged control group) and 13 AD brains were analyzed. An optimized design for sampling, measuring volume by using the Cavalieri principle, and counting the number of neurons by using the optical disector was implemented on 50 microns-thick cresyl-violet sections. The mean total volume of the principal subdivisions of the hippocampal formation (fascia dentata, hilus, CA3-2, CA1, and subiculum) showed a negative correlation with age in normal subjects (r = -0.56, 2P < 0.05), and a 32% mean reduction in the AD group compared with controls (P < 0.001). This finding supports the measurement of the coronal cross-sectional area and the volume of the hippocampal formation in the clinical diagnosis of AD. There was an inverse relationship between the age of normal subjects and the number of neurons in CA1 (r = -0.84, 2P < 0.0001) and subiculum (r = -0.49, 2P < 0.05) but not in other subdivisions. Pronounced AD-related reductions in neuron number were found only in the subiculum and the fascia dentata. Compared with controls, both losses represented 23% of neurons (P < 0.05). These results 1) confirm that AD is a qualitatively different process from normal aging and 2) reveal the regional selectivity of neuron loss within the hippocampal formation in aging and AD, which may be relevant to understanding the mechanisms involved in the neuron loss associated with the two processes.
Adolescent↗
Laminar distribution of neuropeptide Y-immunoreactive neurons in human prefrontal cortex during development.
Neuropeptide Y (NPY) is present in neurons of the adult human cerebral cortex. In view of the reported roles of NPY in the central nervous system in health and during certain disease conditions, we have studied normal development of NPY immunoreactivity (-ir) in the human prefrontal cortex (PFC), Brodmann areas 9 and 46. Twenty-six specimens ranging from the ages of 14 postovulatory weeks to 34 years exhibited patterns that revealed six periods in the development of the laminar distribution and density of NPY-ir neurons. Changes during prenatal and perinatal periods reflect the onset, development, and resolution of the transient fetal telencephalic compartments, including the subplate zone, in which NPY-ir neurons are especially abundant. Before the age of 1 year, the majority of NPY-ir neurons were found in the subplate zone, whereas, after 1 year, the majority were seen in the cortical layers. This is in contrast with the human visual cortex, where the majority of NPY-ir neurons were still located in the white matter. The density of cortical NPY-ir neurons increased in the fifth developmental period (ages 4-7 years), coinciding with the increase of cortical volume and marked progression of cognitive functions. The adult pattern of a relatively low density of cortical NPY-ir neurons was reached in period 6 (from about 8 years), when individual variation also became apparent. Our data point to a protracted maturation of NPY-ir in the human PFC and to different distribution patterns of NPY-ir neurons in different cortical areas.
Adolescent↗
Transient patterns of calbindin-D28k expression in the developing striatum of man.
In fetal and adult human brains, calbindin immunoreactivity (CB-ir) of neostriatal neuropil showed inhomogeneous pattern. A mosaic of CB-ir neuropil patches matching the acetylcholinesterase (AChE)-reactive patches and most of the encapsulated cell-dense islands was distributed in a lighter stained background matrix. During infancy, the pattern of CB expression changed from one of CB-rich patches to one of CB-poor striosomes and rich matrix. Furthermore, we observed a steady development of population of medium-sized neurons in the striatal matrix; in addition, a transient CB-expression was found in cells of the ganglionic eminence and presumably in a subset of striatal interneurons.
Acetylcholinesterase↗
Transient neuronal population of the internal capsule in the developing human cerebrum.
The present study reveals the presence of a distinct group of cells, resembling reticular thalamic neurones, in the internal capsule during fetal development. This cell population rapidly decreases in size during early infancy and few cells are apparent in the 1-year-old infant. Internal capsule cells are well differentiated, multipolar or polymorphous, AChE (acetylcholinesterase)-reactive neurones. The following specific molecular markers were demonstrated in the neurones of the internal capsule: MAP2 (microtubule-associated protein 2), somatostatin, calbindin-D28K and p75 low-affinity NGF (nerve growth factor) receptor. A group of neurones described here corresponds to the perireticular thalamic nucleus found in certain mammalian species, hitherto unidentified in the primate brain, which may play an important role during development.
Acetylcholinesterase↗
Ontogenesis of goal-directed behavior: anatomo-functional considerations.
Recent neuroanatomical and neurophysiological studies in man have revealed ontogenetic events which coincide with broadly defined phases of behavioral and cognitive development. During the early fetal period, early produced neurons make initial synapses which form the basis for the earliest electrical activity of the human brain. The overall immaturity of neuronal connections, in particularly in cortical areas, correlates with the absence of any behavioral pattern or goal-directed movements. In the late fetus and preterm infant, transient accumulation of major afferent pathways, the presence of transient layers (subplate zone) and transient pattern of transmitter-related organization form the neurological basis of cortical electric responses as well as transient behavioral states and sleep patterns. Parallel to the profound structural and chemical reorganization of the human cerebrum during the first 6 postnatal months there is a disappearance of transient behavioral and motor patterns. The previously close spatio-temporal correlation between these events becomes progressively looser. The overproduction of circuitry elements during the subsequent period peaks in associative cortex between 1 and 2 years of age, corresponding to the emergence of skilled actions and cognitive functions. After the elimination of some circuitry elements after the second year of life, the prolonged maturation of goal-directed behavior and the protracted emergence of different cognitive functions correlates with the development plateau of synapse production which can be seen up to 16 years of age. Parallel to the prolonged maturation of postsynaptic elements, there are well defined maturational changes in the chemical properties of associative pyramidal neurons of cortical layer III. These findings correspond to the prolonged maturation of movement-related brain macropotentials as well as other cognition-related potentials, where the last prominent changes were seen after 10 years of age. Although the coincidence of the developmental events does not necessarily mean a causal relationship, the combination of structural and physiological data opens new vistas for the further investigation of the neurobiological basis of goal-directed movement and cognitive behavior.
Adolescent↗
Histochemical localization of nitric oxide synthase in the CNS.
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Amino Acid Oxidoreductases↗
Early areal differentiation of the human cerebral cortex: entorhinal area.
The early cytoarchitectonic specialization and area-specific differentiation of the prospective entorhinal cortex were studied in the postmortem human fetal brains (9.5-13.5 postovulatory weeks). At 10 weeks, using the Golgi method, we saw the appearance of area-specific large neurons (promoter neurons) with widely bifurcating apical dendrites situated at the outer margin of the cortical plate of the prospective entorhinal cortex. The analysis of the serial Nissl-stained sections revealed the concomitant appearance of a one-cell-thick layer (monolayer) at the interface between the cortical plate and the marginal zone and multilaminated spread of the deep part of the cortical plate. This is the earliest sign of area-specific cytoarchitectonic differentiation of all pallial regions characterized by the presence of the typical cortical plate. The first subareal differentiation within the entorhinal cortex begins at 13 postovulatory weeks with uneven development of fiber-rich lamina dissecans, which separates two cellular laminae principals (externa and interna), and with the appearance of characteristic cell islands of the prospective layer II. At rostral levels, cell islands begin to develop in the rostromedial entorhinal area at the subpial depths where large promoter neurons reside. At intermediate levels, both lamina dissecans and lamina principalis interna are well delineated. At caudal levels, lamina principalis interna is continuous with the upper subplate zone of the adjacent neocortex. Both area-specific neurons (promoters) and fiber-rich (afferent) strata develop synchronously during the earliest areal differentiation of the cerebral cortex. The precocious lamination of the cortical plate is the crucial event in the histogenesis of the entorhinal cortex.
Afferent Pathways↗
Attacks on Croatia's hospitals.
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Hospitals↗
Prenatal and perinatal development of the somatostatin-immunoreactive neurons in the human prefrontal cortex.
The earliest somatostatin-immunoreactive (SS-Ir) perikarya of the human fetal frontal cortex appear in the transient subplate zone at 22 weeks of gestation. Around 32 weeks of gestation there is an increase in the number of SS-Ir neurons at the interface between the subplate zone and the cortical plate. The newborn-cortex shows decline in the overall number of SS-Ir neurons parallel to the appearance of SS-Ir neurons in the superficial layers. In conclusion, the subplate neurons are the source of the earliest peptidergic activity in the cortex. Furthermore, the distribution and density of peptidergic neurons undergo significant reorganization during the perinatal development.
Cerebral Cortex↗
Neuroscience in Yugoslavia.
This survey is a personal account of the present status of neuroscience in Yugoslavia within the context of recent upheavals in Eastern Europe. The current situation in Yugoslavia, characterized by the absence of a Federal Ministry of Science and a poor scientific communication between federal states (republics), does not allow a comprehensive overview of neuroscience at the federal level. Even more difficult is to envisage the prospects of Yugoslav neuroscience in the light of European integration. Several problems serve to illustrate the present situation concerning Yugoslav neuroscience. First, the weakness of the self-organization of science in Yugoslavia during the past 20 years is still the most important denominator in the current trend of neuroscience. Second, different Yugoslav republics have significantly different systems of science funding and evaluation, which reflect very plainly different levels of democratic (and socioeconomic) changes that were attained during 1990. Third, due to the different numbers of trained scientists, facilities and equipment, funds and levels of international scientific cooperation there are major differences between republics in the tempo of progress towards real achievements in science. Finally, the present explosive development of neuroscience and the proclamation of the 'Decade of the Brain' will hopefully stimulate Yugoslav neuroscientists to seek better programmes of neuroscience research and to improve the extent and quality of international cooperation.
Animals↗
Structural and histochemical reorganization of the human prefrontal cortex during perinatal and postnatal life.
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Embryonic and Fetal Development↗
Structural basis of the developmental plasticity in the human cerebral cortex: the role of the transient subplate zone.
We correlated neuroanatomical developmental parameters with sequential ultrasonography scans to reveal the structural basis of functional recovery after early focal hypoxic lesions of the human frontal lobe in premature infants. We studied the transient fetal subplate zone in the premotor and prefrontal cortex in premature, newborn, infant, and young adult brains by acetylcholinesterase (AChE) histochemical, Golgi, and immunocytochemical methods. The structural in vivo rearrangements of the cerebral wall after perinatal lesions were studied on serial real-time sector scans (5-MHz transducer). The subplate zone contains "waiting" axons and randomly oriented fetal neurons, its developmental peak is between 22 and 34 weeks of gestation, and it is present in the frontal cortex of newborns and disappears after the sixth postnatal month, but individual subplate-like neurons remain until adulthood. Ultrasonography revealed remarkable structural rearrangements of the cerebral wall when the hypoxic lesion occurred during the developmental peak of the subplate zone: anechoic cavities ("cysts") develop rapidly (within 3 weeks) in premature brains, the rebuilding of these lesions continues after birth, and cavities disappear around the 11th month. We propose that the transient population of "waiting" axons and cells of the subplate zone participate in the structural and functional plasticity of the human cerebral cortex after perinatal brain damage.
Adult↗
Early onset of synapse formation in the human hippocampus: a correlation with Nissl-Golgi architectonics in 15- and 16.5-week-old fetuses.
The developmental status of some potential components of hippocampal circuitry was studied at the time of the emergence of the hippocampal cytoarchitectonic subfields. The laminar distribution of synapses as seen with electron microscopy was correlated with Golgi architectonics in 15- and 16.5-week-old human fetuses. A systematic electron microscopic analysis of the distribution of synapses demonstrated that they were restricted to the two zones bordering the cortical plate, viz. the marginal and subplate zones, which contain dendritic branches of pyramidal and large polymorphous non-pyramidal neurons. The density of synapses (number per unit area) was higher in the marginal zone than in the subplate zone. Most synapses were of the asymmetric axodendritic type, although some were symmetric axodendritic synapses. The possible origins of the axons forming these synapses are discussed. This study demonstrates that the human hippocampus shows an early onset of synapse formation, with a characteristic distribution of synapses in restricted laminae. The finding of early synapse formation is consistent with observations made in other cortical areas during development. The prevalence of synaptogenesis at a superficial level of the cortex seems, however, to be specific to the "archicortex".
Embryonic and Fetal Development↗