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At least 163 records · Page 9Linked to original sources
PubMed2000

HIV-1 coat glycoprotein gp120 induces apoptosis in rat brain neocortex by deranging the arachidonate cascade in favor of prostanoids.

Human immunodeficiency virus type-1 coat glycoprotein gp 120 causes delayed programmed cell death (apoptosis) in rat brain neocortex. Here, we investigated the possible role of the arachidonate cascade and membrane peroxidation in this process. It is shown that gp 120 causes a rapid increase in the activity and expression of the arachidonate-metabolizing enzyme prostaglandin H synthase, paralleled by increased prostaglandin E(2) levels. The selective inhibitor of prostaglandin H synthase indomethacin inhibited enzyme activity, reduced prostaglandin E(2) content, and partially protected neocortex against gp 120-induced apoptosis. Conversely, the activity and expression of the arachidonate-metabolizing enzyme 5-lipoxygenase decreased upon gp 120 treatment, as well as the level of its product, leukotriene B(4). Treatment with gp 120 also reduced membrane lipid peroxidation, and this may be implicated in the execution of programmed cell death. These results suggest that early derangement of the arachidonate cascade in favor of prostanoids may be instrumental in the execution of delayed apoptosis in the brain neocortex of rats.

Animals↗
PubMed2004

A comparative analysis of transcribed genes in the mouse hypothalamus and neocortex reveals chromosomal clustering.

The hypothalamus and neocortex are subdivisions of the mammalian forebrain, and yet, they have vastly different evolutionary histories, cytoarchitecture, and biological functions. In an attempt to define these attributes in terms of their genetic activity, we have compared their genetic repertoires by using the Serial Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus tags with 125,296 neocortical tags, we demonstrate that each structure possesses a different transcriptional profile in terms of gene ontological characteristics and expression levels. Despite its more recent evolutionary history, the neocortex has a more complex pattern of gene activity. Gene identities and levels of gene expression were mapped to their chromosomal positions by using in silico definition of GC-rich and GC-poor genome bands. This analysis shows contrasting views of gene activity on a genome scale that is unique to each brain substructure. We show that genes that are more highly expressed in one tissue tend to be clustered together on a chromosomal scale, further defining the genetic identity of either the hypothalamus or neocortex. We propose that physical proximity of coregulated genes may facilitate transcriptional access to the genetic substrates of evolutionary selection that ultimately shape the functional subdivisions of the mammalian brain.

Animals↗
PubMed2003

Permissive corridor and diffusible gradients direct medial ganglionic eminence cell migration to the neocortex.

Young neurons born in the medial ganglionic eminence (MGE) migrate a long distance dorsally, giving rise to several types of interneurons in neocortex. The mechanisms that facilitate selective dorsal dispersion of MGE cells while restricting their movement ventrally into neighboring regions are not known. Using microtransplantation into fetal brain slices and onto dissociated substrate cells on floating filters (spot assay), we demonstrate that ventral forebrain regions neighboring the MGE are nonpermissive for MGE cell migration, whereas the dorsal regions leading to the neocortex are increasingly permissive. Spot assay experiments using filters with different pore sizes indicate that the permissive factors are not diffusible. We also show that MGE cells respond to chemoattractive and inhibitory factors diffusing from the neocortex and ventromedial forebrain, respectively. We propose that the final extent and regional specificity of MGE cell dispersion is largely dictated by contact guidance through a selectively permissive environment, flanked by nonpermissive tissues. In addition, we propose that chemotactic guidance cues superimposed over the permissive corridor facilitate efficient dorsal migration of MGE cells.

Animals↗
PubMed2006

Attractor dynamics in a modular network model of neocortex.

Starting from the hypothesis that the mammalian neocortex to a first approximation functions as an associative memory of the attractor network type, we formulate a quantitative computational model of neocortical layers 2/3. The model employs biophysically detailed multi-compartmental model neurons with conductance based synapses and includes pyramidal cells and two types of inhibitory interneurons, i.e., regular spiking non-pyramidal cells and basket cells. The simulated network has a minicolumnar as well as a hypercolumnar modular structure and we propose that minicolumns rather than single cells are the basic computational units in neocortex. The minicolumns are represented in full scale and synaptic input to the different types of model neurons is carefully matched to reproduce experimentally measured values and to allow a quantitative reproduction of single cell recordings. Several key phenomena seen experimentally in vitro and in vivo appear as emergent features of this model. It exhibits a robust and fast attractor dynamics with pattern completion and pattern rivalry and it suggests an explanation for the so-called attentional blink phenomenon. During assembly dynamics, the model faithfully reproduces several features of local UP states, as they have been experimentally observed in vitro, as well as oscillatory behavior similar to that observed in the neocortex.

Action Potentials↗
PubMed1998

Long-term potentiation in the neocortex of the adult, freely moving rat.

Neocortical preparations have proven highly resistant to the induction of long-term potentiation (LTP), and we have only recently determined the conditions sufficient for the induction of neocortical LTP in the adult, freely moving rat. The stimulation trains must be spaced and repeated over a period of days in order to reach asymptotic levels of potentiation. Here we show that, within these constraints, the neocortex is actually highly responsive. LTP could be induced with as few as one brief high frequency train per day or with extremely low-intensity stimulation trains. We also provide evidence for a critical role for N-methyl-D-aspartate (NMDA) receptor activation in LTP induction in this preparation, and demonstrate that this LTP is input-specific. Control pathways showed no potentiation effects. LTP was found in a monosynaptic and two polysynaptic components (average latencies to peak: 8.1, 15.2 and 20.0 ms) and in the superimposed population spikes. Although LTP could be induced with one train per day or with low-intensity trains, larger and longer-lasting potentiation effects could be induced by increasing the number of trains delivered per session, the number of sessions over which trains were delivered, or the pulse intensity of the trains. The LTP decayed slowly and was still evident 5 weeks later. Administration of the competitive NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid blocked the induction of LTP in a dose-dependent fashion and appeared to unmask a depression of both the population spikes and a polysynaptic component. These results indicate that the neocortex is highly sensitive to LTP induction procedures, as long as the stimulation trains are spaced and applied over a period of days. They are also consistent with the view that the neocortex must operate with a slow learning rate to reduce interference effects in memory.

Aging↗
PubMed2004

Chemically specific circuit composed of vesicular glutamate transporter 3- and preprotachykinin B-producing interneurons in the rat neocortex.

The third vesicular glutamate transporter, VGLUT3, is distributed in cell bodies of neocortical neurons and axon terminals mainly in the superficial part of layer II/III of the cerebral cortex. We examined the chemical characteristics of VGLUT3-expressing neurons by immunohistochemistry in the rat neocortex. Since the vast majority of VGLUT3-immunoreactive neurons showed immunoreactivities for GABA, preprotachykinin B (PPTB) and cholecystokinin, VGLUT3-immunoreactive neocortical neurons were considered to constitute a subgroup of GABAergic interneurons. VGLUT3-immunoreactive axon terminals were immunopositive for either vesicular GABA transporter (VGAT) or serotonin. These results together with anterograde tracer injection and chemical lesion experiments in the dorsal and median raphe nuclei revealed that the neocortex contains at least two kinds of VGLUT3-laden axon terminals: one is serotonergic and derived from the raphe nuclei, and the other is GABAergic and intrinsic in the neocortex. Furthermore, many VGLUT3/VGAT-immunoreactive terminals formed axon baskets and made axosomatic symmetric synapses on neocortical neurons, most of which were immunoreactive for PPTB. VGLUT3-immunopositive axon baskets surrounded about a half of PPTB-positive and almost all VGLUT3-positive neurons. Thus, VGLUT3-expressing GABAergic interneurons form a chemically specific circuit within the PPTB-producing interneuron group and it is likely that glutamate is used within the chemically specific circuit.

Amino Acid Transport Systems, Acidic↗
PubMed2005

THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex.

THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Since its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 muM induced a robust tonic GABA(A)-mediated current in layer 2/3 neurons. In comparison, only a minute tonic current was induced by mimicking in vivo endogenous GABA levels. Miniature IPSCs were not affected by 1 muM THIP suggesting an extrasynaptic site of action. The EC(50) for THIP was 44 muM. In accordance with the stronger expression of delta-containing receptors in superficial neocortical layers, THIP induced a 44% larger tonic current in layer 2/3 than in layer 5 neurons. Finally, monitoring spontaneously active neocortical neurons, THIP caused an overall depression of inhibitory activity, while enhancing excitatory activity prominently. Our studies suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity.

Analgesics↗
PubMed2003

Changes in neuronal migration in neocortex of connexin43 null mutant mice.

To identify a neural phenotype in connexin43 null mutant mice, electrophysiological properties, intercellular communication and neuronal migration were studied in the developing neocortex. In acute slice preparations from newborn mice, electrophysiological characteristics of cortical and hippocampal neurons were not significantly different between wild type and null mutant mice. However, gap junctional coupling as assessed by fluorescence recovery after photobleaching was significantly attenuated in neocortical brain slices of null mutant mice. To assess neuronal migration, dividing cells were labeled with bromodeoxyuridine (BrdU) on embryonic days 12, 14 and 16, respectively, corresponding to the period of cortical neurogenesis, and the neocortex examined 2 or 3 days after the labeling. BrdU-labeled cells were distributed in the neocortical wall with a significant change in the pattern in the neocortex of the null mutant, where labeled cells accumulated in the intermediate zone or in the inner part of the cortical plate. The result suggests a significant delay in neocortical neuronal migration in the connexin43 null mutants, and a possible role of connexin43 in this process through yet unidentified mechanisms.

Animals↗
PubMed1997

MRI-based morphometric topographic parcellation of human neocortex in trichotillomania.

The purpose of the present study was to test specific hypotheses regarding volumetric changes of the neocortex between 10 female trichotillomania (TTM) subjects and 10 female normal controls. A standard three-dimensional (3-D) brain coordinate system was imposed over each newly acquired native magnetic resonance imaging (MRI) scan for positional normalization and 3-D shape/geometric localization analyses were based on the midpoints of anterior and posterior commissures, and the longitudinal fissure. The brain segmentation method, using well-characterized semiautomated intensity and differential contour algorithms by signal intensity-frequency histograms, was used blind to segment the principal gray and white matter structures. The segmented neocortical ribbon was subdivided into 48 regions (i.e. parcellation units) per hemisphere via a new method of morphometric topographic parcellation. There were no significant volumetric changes of the precentral gyrus, postcentral gyrus, supplementary motor cortex or opercular cortex in TTM patients compared with control subjects. A broader analysis as a hypothesis-generating post-hoc effort showed that TTM subjects exhibited significantly reduced left inferior frontal gyrus volume of 27% (t = 2.21, d.f. = 18, P = 0.04) and enlarged right cuneal cortex volume of 40% (t = -2.30, d.f. = 18, P = 0.03) compared to normal controls. This is the first report of a structural neocortex abnormality in TTM. Results are discussed in terms of the behavioral specialization of these two brain neocortical regions and the complex interractions between visual and sensorimotor cortices. The results also showed the feasibility of the MRI-based morphometric topographic parcellation for investigation of the human neocortex in neuroscience research.

Adult↗
PubMed2005

Aberrant trajectory of thalamocortical axons associated with abnormal localization of neurocan immunoreactivity in the cerebral neocortex of reeler mutant mice.

We examined the molecular mechanisms underlying the formation of the thalamocortical pathway in the cerebral neocortex of normal and reeler mutant mice. During normal development of the mouse neocortex, thalamic axons immunoreactive for the neural cell adhesion molecule L1 rarely invaded the cortical plate and ran centered in the subplate which is immunoreactive for neurocan, a brain-specific chondroitin sulfate proteoglycan. On the other hand, in homozygous reeler mutant mice, thalamic axons took an aberrant course to run obliquely through the cortical plate. Injection of bromodeoxyuridine at embryonic day 11 specifically labeled subplate neurons in normal mice, whilst in the reeler neocortex it labeled cells scattered in the cortical plate as well as in the superficial layer (superplate). Neurocan immunoreactivity was associated with the bromodeoxyuridine-positive cells in the superplate, as well as being present in oblique bands within the cortical plate, along which L1-bearing thalamic axons preferentially ran. The present results support our previous hypothesis proposed for normal rats that a heterophilic molecular interaction between L1 and neurocan is involved in determining the thalamocortical pathway within the neocortical anlage [T. Fukuda et al. (1997) Journal of Comparative Neurology, 382, 141-152].

Animals↗
PubMed2004

Enhanced anandamide degradation is associated with neuronal apoptosis induced by the HIV-1 coat glycoprotein gp120 in the rat neocortex.

Human immunodeficiency virus type-1 coat glycoprotein gp120 causes delayed apoptosis in rat brain neocortex. Here, we investigated the possible role of the endocannabinoid system in this process. It is shown that gp120 causes a time-dependent increase in the activity and immunoreactivity of the anandamide (AEA)-hydrolyzing enzyme fatty acid amide hydrolase (FAAH), paralleled by increased activity of the AEA membrane transporter and decreased endogenous levels of AEA. The AEA-synthesizing phospholipase D and the AEA-binding receptors were not affected by gp120. None of the changes induced by gp120 in the cortex were induced by bovine serum albumin, nor were they observed in the hippocampus of the same animals. Also, the activity of 5-lipoxygenase, which generates AEA derivatives able to inhibit FAAH, decreased down to approximately 25% of the control activity upon gp120 treatment, due to reduced protein level ( approximately 45%). In addition, the FAAH inhibitor methyl-arachidonoyl fluorophosphonate significantly reduced gp120-induced apoptosis in rat brain neocortex, whereas selective blockers of AEA membrane transporter or of AEA-binding receptors were ineffective. Taken together, these results suggest that gp120, by activating FAAH, decreases endogenous levels of AEA, and the latter effect seems instrumental in the execution of delayed neuronal apoptosis in the brain neocortex of rats.

Amidohydrolases↗
PubMed2001

Cell proliferation without neurogenesis in adult primate neocortex.

A recent assertion that new neurons are continually added to the neocortex of adult macaque monkeys has profound implications for understanding the cellular mechanisms of higher cognitive functions. Here we searched for neurogenesis in adult macaques by using immunofluorescent triple labeling for the DNA-replication indicator, bromodeoxyuridine (BrdU), and neuronal and glial cell markers. Although numerous BrdU-labeled cells were distributed throughout the cerebral wall, including the neocortex, these were identified as nonneuronal cells; evidence for newly generated neurons was limited to the hippocampus and olfactory bulb. Thus, our results do not substantiate the claim of neurogenesis in normal adult primate neocortex.

Animals↗
PubMed2000

Regulation of area identity in the mammalian neocortex by Emx2 and Pax6.

The contribution of extrinsic and genetic mechanisms in determining areas of the mammalian neocortex has been a contested issue. This study analyzes the roles of the regulatory genes Emx2 and Pax6, which are expressed in opposing gradients in the neocortical ventricular zone, in specifying areas. Changes in the patterning of molecular markers and area-specific connections between the cortex and thalamus suggest that arealization of the neocortex is disproportionately altered in Emx2 and Pax6 mutant mice in opposing manners predicted from their countergradients of expression: rostral areas expand and caudal areas contract in Emx2 mutants, whereas the opposite effect is seen in Pax6 mutants. These findings suggest that Emx2 and Pax6 cooperate to regulate arealization of the neocortex and to confer area identity to cortical cells.

Animals↗
PubMed1999

Effects of osmotic stress on dextran diffusion in rat neocortex studied with integrative optical imaging.

Effects of osmotic stress on dextran diffusion in rat neocortex studied with integrative optical imaging. This study investigated how dextran (Mr = 3,000) diffused in rat cortical slices when the osmolarity of the bathing artificial cerebrospinal fluid was altered by varying the NaCl content. The apparent diffusion coefficient, D*, was measured in the neocortex region using fluorescent molecules and the integrative optical imaging (IOI) method. The main results were: 1) the value of D* in rat neocortex in the isotonic (300 mOsm) artificial cerebrospinal fluid at 34 degrees C was D* = 0.68 +/- 0. 01 x 10(-6) cm2 s-1 (mean +/- SE, n = 78) and it could be changed within minutes by varying the extracellular osmolarity. 2) Hypotonic stresses up to -100 mOsm decreased D* by 35% and were fully reversible when the slices were returned to the isotonic medium. Further hypotonic stress to -150 mOsm caused further decrease in D* but after removal of the stress, D* overshot its control value. 3) Hypertonic stress of +50 mOsm increased D*, but the maximum reversible increase in D* was only 15%. Further hypertonic stress (to +200 mOsm) did not cause any further increase in D* and, after removal of the stress, D* undershot the control value. The changes in D* are thought to be related to volume changes of cells in tissue: hypotonic solutions caused cell swelling, resulting in reduced extracellular space and compressed extracellular matrix so that the dextran diffusion was more hindered. Hypertonic solutions had the opposite effect. Recordings of extracellular field potentials in the hippocampal CA1 region demonstrated that, on return to the isotonic solution after exposure to an extreme hypotonic or hypertonic stress, the neurons retained their ability to generate synaptic responses.

Animals↗
PubMed2000

Neurochemical and cellular specializations in the mammalian neocortex reflect phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls.

Most of the available data on the cytoarchitecture of the cerebral cortex in mammals rely on Nissl, Golgi, and myelin stains and few studies have explored the differential morphologic and neurochemical phenotypes of neuronal populations. In addition, the majority of studies addressing the distribution and morphology of identified neuronal subtypes have been performed in common laboratory animals such as the rat, mouse, cat, and macaque monkey, as well as in postmortem analyses in humans. Several neuronal markers, such as neurotransmitters or structural proteins, display a restricted cellular distribution in the mammalian brain, and recently, certain cytoskeletal proteins and calcium-binding proteins have emerged as reliable markers for morphologically distinct subpopulations of neurons in a large number of mammalian species. In this article, we review the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of the neurofilament protein triplet, a component of the neuronal cytoskeleton, to provide an overview of the presence and cellular typology of these proteins in the neocortex of various mammalian taxa. Considering the remarkable diversity in gross morphological patterns and neuronal organization that occurred during the evolution of mammalian neocortex, the distribution of these neurochemical markers may help define taxon-specific patterns. In turn, such patterns can be used as reliable phylogenetic traits to assess the degree to which neurochemical specialization of neurons, as well as their regional and laminar distribution in the neocortex, represent derived or ancestral features, and differ in certain taxa from the laboratory species that are most commonly studied.

Animals↗
PubMed2007

A comparison study of the vertical bias of pyramidal cells in the hippocampus and neocortex.

In this study, we employed morphometric image analysis of the hippocampus proper and temporal lobe neocortex in postmortem tissue to determine vertical bias quantified as Deltatheta, angular dispersion, as well asan index of alignment of cellular elements relative to the radial plane. The radial alignment of cellular elements was consistent with a minicolumnar organization of the cortex. Photomicrographs were taken of the left-hemisphere hippocampal CA3/1 subfields of 13 fetal subjects ranging in gestational age from 19 weeks to 36 weeks and 19 normal individuals aged 4 months to 98 years. For comparison, micrographs from the temporal lobe (Brodmann areas 21 and 22) were similarly processed for layers III and V, where the x-axes of the transformed coordinate system were taken to be the layer III/IV and IV/V borders, respectively. Computerized image analysis measurements of the angular dispersion for the temporal lobe region and hippocampus proper differed significantly within the same brains (p < 0.001). The neocortical layer III exhibited the highest values for Deltatheta, indicating a high degree of columnar organization. Values for Deltatheta in the hippocampal CA subfields were lower but demonstrated significance for the radial alignment of neurons in this area. Values for Deltathetain layer V were intermediate between those of layer III and the hippocampus, consistent with increasing degrees of radial columnar organization of infragranular layers of the neocortex in comparison with the hippocampus and of supragranular in comparison with infragranular neocortical layers. Pyramidal cell arrays within allocortical areas and the neocortex constitute different modular arrangements. This morphological variability may be the expression of evolutionary differences in cortical development.

Adolescent↗
PubMed2006

Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex.

The transcription factor STAT3 promotes astrocytic differentiation of neural precursor cells (NPCs) during postnatal development of the mouse neocortex, but little has been known of the possible role of STAT3 in the embryonic neocortex. We now show that STAT3 is expressed in NPCs of the mouse embryonic neocortex and that the JAK-STAT3 signaling pathway plays an essential role in the maintenance of NPCs by fibroblast growth factor 2. Conditional deletion of the STAT3 gene in NPCs reduced their capacity to form neurospheres in vitro, as well as promoted neuronal differentiation both in vitro and in vivo. Furthermore, STAT3 was found to maintain NPCs in the undifferentiated state in a non-cell-autonomous manner. STAT3-dependent expression of the Notch ligand Delta-like1 (DLL1) appears to account for the non-cell-autonomous effect of STAT3 on NPC maintenance, as knockdown of DLL1 by RNA interference or inhibition of Notch activation with a gamma-secretase inhibitor abrogated the enhancement of neurosphere formation by STAT3. Our results reveal a previously unrecognized mechanism of interaction between the JAK-STAT3 and DLL1-Notch signaling pathways, as well as a pivotal role for this interaction in maintenance of NPCs during early neocortical development.

Animals↗
PubMed2003

Choline acetyltransferase-containing neurons in the human parietal neocortex.

A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

Aged↗