Biomedical subjects

H Supèr

Publications and source records attributed to H Supèr.

11 recordsLinked to original sources

PubMed2000

The early development of thalamocortical and corticothalamic projections in the mouse.

The initial ingrowth of corticothalamic and thalamocortical projections was examined in mice at embryonic and perinatal stages. Fibers, in fixed brains, were labeled with the carbocyanine dye 1, 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocianine perchlorate (DiI). By E13, the corticofugal fibers had entered the lowest intermediate zone through which they ran, turned over the corpus striatum, and left the cortex. The fibers were arranged in scattered bundles throughout the corpus striatum. At E14 corticofugal axons reached the internal capsule and at E14.5-E15 they established contact within the thalamus. Meanwhile, the thalamocortical afferents reached the neocortex at E13. At this time fibers ran tangentially within the intermediate zone, immediately underneath the cortical plate. By E14, the fibers had started to invade the subplate and, by E15, thalamocortical fibers had begun their radial growth into the cortex. Such radial growth proceeded steadily, invading each cortical layer as it differentiated cytoarchitectonically from the dense cortical plate. The first retrogradely labeled cells were detected at the cortical plate at E15. By the day of birth (E20), thalamocortical fibers had formed a dense branching system within layers VI and V. Our observations indicate that, in mice, the thalamic axons reach the cortex before corticothalamic projections enter the thalamic nuclei. Moreover, the results suggest that the pathway followed by each fiber system is different. By DiI injections into the internal capsule we have also determined that subplate cells are the first to send axons to the thalamus.

Animals↗

PubMed2000

The role of primary visual cortex (V1) in visual awareness.

In the search for the neural correlate of visual awareness, much controversy exists about the role of primary visual cortex. Here, the neurophysiological data from V1 recordings in awake monkeys are examined in light of two general classes of models of visual awareness. In the first model type, visual awareness is seen as being mediated either by a particular set of areas or pathways, or alternatively by a specific set of neurons. In these models, the role of V1 seems rather limited, as the mere activity of V1 cells seems insufficient to mediate awareness. In the second model type, awareness is hypothesized to be mediated by a global mechanism, i.e. a specific kind of activity not linked to a particular area or cell type. Two separate versions of global models are discussed, synchronous oscillations and spike rate modulations. It is shown that V1 synchrony does not reflect perception but rather the horizontal connections between neurons, indicating that V1 synchrony cannot be a direct neural correlate of conscious percepts. However, the rate of spike discharges of V1 neurons is strongly modulated by perceptual context, and these modulations correlate very well with aspects of perceptual organization, visual awareness, and attention. If these modulations serve as a neural correlate of visual awareness, then V1 contributes to that neural correlate. Whether V1 plays a role in the neural correlate of visual awareness thus strongly depends on the way visual awareness is hypothesized to be implemented in the brain.

Animals↗

PubMed1998

Involvement of distinct pioneer neurons in the formation of layer-specific connections in the hippocampus.

During neural development, specific recognition molecules provide the cues necessary for the formation of initial projection maps, which are reshaped later in development. In some systems, guiding cues for axonal pathfinding and target selection are provided by specific cells that are present only at critical times. For instance, the floor plate guides commissural axons in the spinal cord, and the subplate is involved in the formation of thalamocortical connections. Here we study the development of entorhinal and commissural connections to the murine hippocampus, which in the adult terminate in nonoverlapping layers. We show that two groups of pioneer neurons, Cajal-Retzius cells and GABAergic neurons, form layer-specific scaffolds that overlap with distinct hippocampal afferents at embryonic and early postnatal stages. Furthermore, at postnatal day 0 (P0)-P5, before the dendrites of pyramidal neurons develop, these pioneer neurons are preferential synaptic targets for hippocampal afferents. Birthdating analysis using 5'-bromodeoxyuridine (BrdU) pulses showed that most such early-generated neurons disappear at late postnatal stages, most likely by cell death. Together with previous studies, these findings indicate that distinct pioneer neurons are involved in the guidance and targeting of different hippocampal afferents.

Aging↗

PubMed1998

The functions of the preplate in development and evolution of the neocortex and hippocampus.

Recently, it has been shown that the early developmental organization of the archicortical hippocampus resembles that of the neocortex. In both cortices at embryonic stages, a preplate is present, which is split by the formation of the cortical plate into a marginal zone and a subplate layer. The pioneer neurons of the preplate are believed to form a phylogenetically ancient cortical structure. Neurons in these preplate layers are the first postmitotic neurons and have important roles in the development of the cerebral cortex. Cajal-Retzius cells in the marginal zone regulate the phenotype of radial glial cells and may direct neuronal migration establishing the inside-out gradient of corticogenesis. Furthermore, pioneer neurons form the initial axonal connections with other (sub)cortical structures. A significant difference between the hippocampus and neocortex, however, is that in the hippocampus, most afferents are guided by the pioneer neurons in the prominent marginal zone, while in the neocortex most ingrowing afferent axons enter via the subplate. At later developmental periods, most pioneer neurons disappear by cell death or transform into other neuronal shapes. Here, we review the early developmental organization of the mammalian cerebral cortex (both neocortex and hippocampus) and discuss the functions and fate of pioneer neurons in cortical development, in particular that of Cajal-Retzius cells. Evaluating the developmental properties of the hippocampus and neocortex, we present the hypothesis that the distribution of the main ingrowing afferent systems in the developing neocortex, which differs from the one in the hippocampal region, may have enabled the specific evolution of the neocortex.

Animals↗

PubMed1998

Feedforward, horizontal, and feedback processing in the visual cortex.

The cortical visual system consists of many richly interconnected areas. Each area is characterized by more or less specific receptive field tuning properties. However, these tuning properties reflect only a subset of the interactions that occur within and between areas. Neuronal responses may be modulated by perceptual context or attention. These modulations reflect lateral interactions within areas and feedback from higher to lower areas. Recent work is beginning to unravel how horizontal and feedback connections each contribute to modulatory effects and what the role of these modulations is in vision. Whereas receptive field tuning properties reflect feedforward processing, modulations evoked by horizontal and feedback connections may reflect the integration of information that underlies perception.

Animals↗

PubMed1997

Survival of Cajal-Retzius cells after cortical lesions in newborn mice: a possible role for Cajal-Retzius cells in brain repair.

Transient Cajal-Retzius (CR) cells in layer I of the mammalian cerebral cortex are the first postmitotic neurons and they are believed to play a role in neuronal migration and lamination during cortical development. Freezing insults to the cortex of newborn mice produce cortical malformations similar to those observed in human brain disorders. Here we have used calretinin immunostaining to investigate the response of CR cells to freezing lesions of the cortical surface. Shortly after injury, CR cells disappeared from the lesioned zone. Moreover, CR cells located near the lesioned area adopted extremely fusiform shapes. At later postnatal stages (P12), CR cells were still abundant in layer I of the lesioned zone, in contrast to their almost complete loss in control animals. These results show that CR cells survive for longer developmental periods following cortical injury. Furthermore, the initial loss and later re-appearance of CR cells suggest that these neurons might migrate tangentially from the cortical areas surrounding the lesioned zone. These findings imply a role for CR cells in brain repair after cortical injury during development.

Animals↗

PubMed1997

Degeneration of Cajal-Retzius cells in the developing cerebral cortex of the mouse after ablation of meningeal cells by 6-hydroxydopamine.

In the central nervous system, the neurotoxic drug 6-hydroxydopamine (6-OHDA) selectively deletes central catecholaminergic neurons and meningeal cells. Meningeal cells are known to contribute to brain development and their specific degeneration leads to disorganized neuronal positioning. We have analyzed whether a particular population of cortical pioneer neurons, the Cajal-Retzius (CR) cells, which lie just below meningeal cells, is also affected by 6-OHDA treatment. We show that application of 6-OHDA to the cortical surface leads to a rapid degeneration of CR cells, without affecting other cortical neurons. The ablation of CR cells was prevented by normetanephrine, which blocks the 6-OHDA uptake into meningeal cells. These results indicate that the disappearance of CR cells after 6-OHDA treatment may be a result of the ablation of the meningeal cells and suggest a trophic dependence of CR cells upon meningeal cells.

Animals↗

PubMed1996

Differential survival of Cajal-Retzius cells in organotypic cultures of hippocampus and neocortex.

Cajal-Retzius (CR) cells are transient, pioneer neurons of layer I of the cortex that are believed to play essential roles in corticogenesis, e.g., in neuronal migration and synaptogenesis. Here we have used calretinin immunostaining to study the characteristics, survival, and fate of CR cells in single organotypic slice cultures of mouse neocortex and hippocampus deprived of their extrinsic afferents. In neocortical explants, CR cells were observed after 1-3 d in vitro (DIV), but they disappeared after 5-7 DIV, which is similar to their time of degeneration in vivo. The disappearance of CR cells in neocortical slices was prevented by incubation with tetrodotoxin and the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione but not by 2-amino-5-phosphonopentanoic acid, suggesting that neuronal activity and non-NMDA glutamate receptors may trigger CR cell death in the neocortex. In contrast to the situation in vivo, in which many hippocampal CR cells disappear at approximately the third postnatal week, CR cells survived in single hippocampal cultures after long incubation times (31 DIV), with their morphology essentially unaltered. In contrast, fewer CR cells were found when hippocampal slices were cocultured with explants from the entorhinal cortex. Because CR cells are transient synaptic targets for entorhinohippocampal afferents, these findings suggest a role for entorhinal afferents in the degeneration of CR cells in the hippocampus. In conclusion, this study shows different survival properties of CR cells in organotypic slice cultures of hippocampus and neocortex, and it suggests that different mechanisms are involved in the regulation of the process of naturally occurring CR cell death in the two cortical regions.

Afferent Pathways↗

PubMed1995

Migrating neurons in the developing cerebral cortex of the mouse send callosal axons.

The presence of migrating callosal neurons during the development of the murine cerebral cortex was studied using biocytin and the lipophilic dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate as retrograde tracers. After injections of biocytin in the presumptive somatosensory cortex of newborn mice which were analysed one day later, many anterogradely labelled fibres coursed towards the contralateral hemisphere through the corpus callosum. Retrogradely labelled callosal cells were also observed. Most callosal neurons corresponded to immature pyramidal cells. In addition, a few biocytin-labelled callosal neurons displayed extremely fusiform shapes, vertical orientation and a short, single process emerging from the apical side of the perikaryon. At the electron microscopic level, these cells had features identical to those described for migrating callosal neurons. Twenty-four hours after birth, these migrating neurons were almost exclusively observed in the upper, dense aspect of the cortical plate (presumptive layers II-III) and only very exceptionally in the infragranular layers. No retrogradely labelled cell resembling migrating neurons were noticed after injections on postnatal days 2 or 5. To study migrating callosal neurons at embryonic stages, crystals of the lipophilic dye were injected in the corpus callosum or the contralateral white matter in embryos aged 17, 18 and 19 days, corresponding to the initial development of the corpus callosum in mice. Whereas callosal migrating neurons were not detected at embryonic days 17 and 18, injections of the lipophilic dye on embryonic day 19 revealed the presence of labelled migrating neurons in the infragranular layers. To corroborate further that these cells are migrating neurons, [3H]thymidine was administered on embryonic days 16 and 17, and labelled mice were injected with biocytin on embryonic day 19 or the first postnatal day. Retrogradely labelled callosal neurons resembling migrating neurons were autoradiographically labelled. These results indicate that the specification of certain neuronal types and the emergence of their cell type-specific characteristics occur shortly after postmitotic neurons leave the ventricular zone, before being positioned within the cortical plate.

Animals↗

PubMed1994

The organization of the embryonic and early postnatal murine hippocampus. II. Development of entorhinal, commissural, and septal connections studied with the lipophilic tracer DiI.

We have analyzed the early development of the main hippocampal afferents in the mouse. Following injections of the lipophilic tracer 1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in the entorhinal cortex, entorhinal axons were observed for the first time in the hippocampus at E15, in the white matter. At E17, entorhinal fibers arborized within the stratum lacunosum-moleculare. At subsequent stages entorhinal axons formed dense networks that were restricted to their appropriate termination zone in the lacunosum-moleculare. The first axons invading the fascia dentata were noticed at E19, their density increasing at later stages. These axons were mainly present in the outer molecular layer. This onset of entorhinohippocampal projections was corroborated by retrograde labeling data after injections in the hippocampus. Commissural fibers first entered the contralateral hippocampus at E18, their number increasing at the following stages. Commissural axons arborized within the stratum oriens and radiatum in the hippocampus proper. In the fascia dentata, the earliest commissural fibers were seen at P2, terminating in the inner zone of the molecular layer and in the hilus. We conclude that developing entorhinal and commissural axons show a high degree of laminar specificity from the earliest stages of formation, which is compatible with the notion that distinct subsets of early maturing neurons populating the hippocampal plexiform layers may attract particular fiber systems. Hippocamposeptal fibers develop at E15, before the first septal fibers can be detected in the hippocampus. These early hippocamposeptal fibers originated from nonpyramidal neurons and terminated in the medial septal area, which is the main source of septal afferents to the hippocampus. In contrast, septohippocampal fibers were not seen in the hippocampus until E17. At perinatal stages, the hippocamposeptal connection reshapes, sending axons to the dorsolateral septal area as the innervation of the medial septum becomes less conspicuous. This sequence suggests that hippocampal neurons pioneer the formation of septohippocampal connections.

Animals↗

PubMed1994

Organization of the embryonic and early postnatal murine hippocampus. I. Immunocytochemical characterization of neuronal populations in the subplate and marginal zone.

Immunocytochemical techniques were used to characterize the neuronal populations in the hippocampal subplate and marginal zone from embryonic day 13 (E13) to postnatal day 5 (P5). Sections were processed for the visualization of microtubule-associated protein 2 (MAP2) and other antigens such as neurotransmitters, neuropeptides, calcium-binding proteins and a synaptic antigen (Mab SMI81). At E13-E14, only the ventricular zone and the primitive plexiform layer were recognized. Some cells in the later stratum displayed MAP2-, gamma-aminobutyric acid (GABA)- and calretinin immunoreactivities. From E15 onwards, the hippocampal and dentate plates became visible. Neurons in the plexiform layers were immunoreactive at E15-E16, whereas the hippocampal and dentate plates showed immunostaining two or three days later. Between E15 and E19 the following populations were distinguished in the plexiform layers: the subventricular zone displayed small neurons that reacted with MAP2 and GABA antibodies; the subplate (prospective stratum oriens) was poorly populated by MAP2- and GABA-positive cells; the inner marginal zone (future stratum radiatum) was heavily populated by multipolar GABAergic cells; the outer marginal zone (stratum lacunosum-moleculare) displayed horizontal neurons that showed glutamate- and calretinin immunoreactivities, their morphology being reminiscent of neocortical Cajal-Retzius cells. Thus, each plexiform layer was populated by a characteristic neuronal population whose distribution did not overlap. Similar segregated neuronal populations were also found in the developing dentate gyrus. At perinatal stages, small numbers of neurons in the plexiform layers began to express calbindin D-28K and neuropeptides. During early postnatal stages, neurons in the subplate and inner marginal zones were transformed into resident cells of the stratum oriens and radiatum, respectively. In contrast, calretinin-positive neurons in the stratum lacunosum-moleculare disappeared at postnatal stages. At E15-E19, SMI81-immunoreactive fibers were observed in the developing white matter, subplate and outer marginal zone, which suggests that these layers are sites of early synaptogenesis. At P0-P5, SMI81 immunoreactivity became homogeneously distributed within the hippocampal layers. The present results show that neurons in the hippocampal subplate and marginal zones have a more precocious morphological and neurochemical differentiation than the neurons residing in the principal cell layers. It is suggested that these early maturing neurons may have a role in the targeting of hippocampal afferents, as subplate cells do in the developing neocortex.

Animals↗