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PubMed1977

A comparison of the effects of prior cold incubation on cerebral cortex function in a hibernator (Cricetus auratus) and a non-hibernator (Cavia porcellus)--II. High energy phosphate levels in cerebral cortex slices after in vitro cold incubation.

1. ATP and CP levels were measured in brain slices from golden hamster and guinea pig after varying periods of cold storage and subsequent incubation at 37 degrees C in the presence and absence of K+ salts. 2. ATP and CP levels were maintained at higher levels in hamster tissue. 3. The results are discussed in relation to the ability of a hibernator to transform and transport chemical energy at low temperatures.

Adenosine Triphosphate↗
PubMed1999

Neurons with choline acetyltransferase immunoreactivity and mRNA are present in the human cerebral cortex.

We examined the cerebral cortex of five autopsied individuals without neurological and psychiatric diseases by immunohistochemistry using an anti-human recombinant choline acetyltransferase (ChAT) polyclonal antibody and in situ hybridization with 35S-labeled human ChAT riboprobes. The immunohistochemistry detected positive neurons which were medium-sized or large pyramidal neurons located predominantly in layers III and V. The density of such neurons was higher in the motor and secondary sensory areas than in other cortical areas; the immunoreactive neurons in layer V were more densely distributed in the motor area and those in layer III were distributed in the secondary sensory areas. Positively stained, non-pyramidal neurons were observed in the superficial layer of the cingulate gyrus and parahippocampus. No immunoreactive neurons were found in the primary sensory areas. The in situ hybridization detected some neurons with signals for ChAT mRNA in the cerebral cortex, most of which were distributed in layer V of the motor area and in layer III of the secondary visual area. These results indicate that the human cerebral cortex contains cholinergic neurons and displays regional and laminal variations in their distribution.

Autopsy↗
PubMed1989

Time course of effects of unilateral lesions of the nucleus basalis of Meynert on glucose utilization by the cerebral cortex. Positron tomography in baboons.

In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices. The animal with the most limited histological lesion showed the least decrease in both ChAT activity and CMRGlu. There was a highly significant linear correlation between the regional cortical decreases in CMRGlu (early postlesion data) and in ChAT activity. These results indicate that cholinergic deafferentation induces a proportional metabolic depression in the cortex. However, compensatory mechanisms operate to restore the cortical metabolic activity gradually despite sustained cholinergic denervation, pointing to pre- and/or postsynaptic adaptation (plasticity). Moreover, unilateral NbM lesions also induced a significant reduction in contralateral CMRGlu, which also demonstrated recovery. Several mechanisms are discussed to explain this contralateral effect, but the most likely implicates a transcallosal depression of function as a result of ipsilateral effects of the NbM lesion. These metabolic effects of cholinergic deafferentation in the primate provide new insight into the mechanisms of cortical dysfunction, and the recovery thereof, following subcortical lesions. In addition, our findings have some relevance to the cortical consequences of cholinergic deafferentation observed in dementia of Alzheimer type.

Animals↗
PubMed1994

The intrinsic geometry of the cerebral cortex.

The mammalian cerebral cortex is a profoundly convoluted six-layered surface. The expansion of the cortex during evolution appears to be due to an increase in the number of functional units as opposed to an increase in the complexity of the units. Geometric similarity predicts that cortical area should increase in proportion to the 2/3 power of cortical volume. Allometric analysis has shown that in fact cortical area increases as a nearly linear function of cortical volume. This can be understood by appreciating that smaller brains tend to be smooth (lissencephalic) and larger brains fissured (gyrencephalic). This process of fissuration has reached its modern terrestrial limit in the human brain where the majority of the cortical surface is hidden within folds. The thickness of the cortex (2-3 mm) is small compared to its area (2000-2500 cm2) so the application of the techniques of differential geometry (the mathematics of idealized surfaces) is justified. Geometric properties of surfaces fall into two categories: intrinsic properties (which are invariant under folding of the surface, e.g. distances measured on the surface) and extrinsic properties (pure folding). The extrinsic geometry of the cortex determines the anatomical appearance of the cortex and the shape of the white matter. The intrinsic curvature of the cortex affects the relative position of functional areas and the spread of activity within the surface itself. A cortical surface has been reconstructed from cross-sections. Analysis of this surface has shown that the cortex has significant intrinsic curvature and hence it is wrong to regard it as merely a crumpled bag. The particular geometry observed is such that the surface is peculiarly "close together". Theoretical considerations and simulations suggest that the intrinsic geometry may have a significant effect on: the necessity of non-uniform growth in models of cortical development; the location of integrative areas; and the synchronization of neuronal firing. It is suggested that intrinsic descriptions of the cortex may prove more natural than extrinsic ones.

Anthropometry↗
PubMed2004

[Molecular mechanisms of neuronal connective tissue genesis during the course of cerebral cortex development].

The cerebral cortex constitutes one of the most complex structures in our brain. In correlation with its elaborate functions, it is characterized by the great complexity of its neuronal connections, but the mechanisms responsible for the generation of these connections remain poorly known. We have recently initiated the characterization of a new multigenic family of axon guidance factors, the ephrin/Eph gene family, during the development of neuronal connections in the mouse cortex. Combining expression studies, in vitro guidance essays, and in vivo analysis of mutant mice, enabled us to demonstrate the critical role of ephrin/Eph genes in the development of cortical networks. Mutant mice for ephrin/Eph genes display a topographic distortion of their cortical somatosensory map, as well as ectopic projections from the motor thalamus to the somatosensory cortex. The identification of factors like ephrins, capable to (re)specify the pattern of neuronal connections, has implications for our understanding of pathological brain development (epilepsy, abnormal movements, psychiatric diseases), and in the perspective of the rational design of cell therapies of neurodegenerative diseases.

Animals↗
PubMed2005

[A case of progressive multifocal leukoencephalopathy presenting white matter MRI lesions extending over the cerebral cortex and a marked decrease in cerebral blood flow on SPECT, and associated with HTLV-I infection].

We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal < 102) was increased, JC virus DNA was detected by PCR, and anti-HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein antibodies revealed the existence of JC virus in biopsied brain specimens, and these findings were consistent with PML. Her symptoms such as motor aphasia, cognitive dysfunction and left hemiparesis were subacutely progressive, and she developed akinetic mutism two weeks after admission. Since the efficacy of cytosine arabinoside for PML has been reported, she was administered 80 mg/day of the drug for five days. After treatment, her communication function was mildly improved but the efficacy was transient. Since it has been reported that HTLV-I, as well as HIV, activates the JC virus promoter and its proliferation, the latent infection of HTLV-I in the central nervous system (CNS) in this case might have stimulated the JC virus proliferation, promoting lesion extension over the cerebral cortex. There have been only a few reports of broad decreases in CBF by SPECT in PML patients. Further MRI and SPECT studies on PML patients are therefore necessary to evaluate the significance of HTLV-I in promoting the JC virus infiltration into the CNS.

Aphasia, Broca↗
PubMed1994

Subplate pioneers and the formation of descending connections from cerebral cortex.

The adult cerebral cortex extends axons to a variety of subcortical targets, including the thalamus and superior colliculus. These descending projections are pioneered during development by the axons of a transient population of subplate neurons (McConnell et al., 1989). We show here that the descending axons of cortical plate neurons appear to be delayed significantly in their outgrowth, compared with those of subplate neurons. To assess the possible role of subplate neurons in the formation of these pathways, subplate neurons were ablated during the embryonic period. In all cases, an axon pathway formed from visual cortex through the internal capsule and into the thalamus. In half of all cases, however, cortical axons failed to invade their normal subcortical targets. In the other half, targets were innervated normally. Subplate neurons are therefore likely to provide important cues that aid the process by which cortical axons grow toward, select, and invade their subcortical targets.

Afferent Pathways↗
PubMed1995

Vasopressin binding in the cerebral cortex of the Mongolian gerbil is reduced by transient cerebral ischemia.

In Mongolian gerbils, the content of vasopressin in the cerebral cortex, the striatum, and the hypothalamus is increased after induction of acute cerebral ischemia. We used an iodinated vasopressin analogue and light microscopic autoradiography to study the distribution of vasopressin V1 receptors in the brain of adult male gerbils and to evaluate the effects of a transient bilateral cerebral ischemia (6 minutes) on the density of this receptor population. The animals were killed immediately or 10, 30, or 100 hours after transient bilateral occlusion of the common carotid arteries. In control animals, specific [125I]-VPA binding sites were present in various structures of the brain (olfactory bulb, anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis, median preoptic area, ventral pallidum, substantia innominata, amygdala, thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling was detected in the cerebral cortex, layers 5-6. After 30-100 hours of survival time following ischemia there was a marked decrease in [125I]-VPA binding site density in these cerebral cortex layers. To a lesser degree, a decrease was also detected in the lateral septal nucleus. In contrast, labeling in other noncortical structures remained unchanged. All animals with 100 hours recovery showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition, ischemia induced concomitant and proliferative changes in cortical and hippocampal astrocytes assessed by glial fibrillary acid protein immunoreactivity. These observations indicate a role for vasopressin in the cerebral cortex either on neurons or on glial cells and the modulation of vasopressin receptor expression by transient cerebral ischemia.

Animals↗
PubMed1990

Somatostatin inhibition of VIP- and isoproterenol-stimulated cyclic AMP accumulation in dissociated cells from rat cerebral cortex.

Freshly dissociated cerebral cortex cells from adult rats have been used in the present study to determine if dual regulation of cyclic AMP levels by inhibitory and stimulatory agents can be expressed in the mature brain. Somatostatin, an inhibitory agent, barely affected the basal cyclic AMP metabolism while vasoactive intestinal peptide (VIP) and isoproterenol, two stimulatory agents enhanced cyclic AMP production. However, this increase was depressed by somatostatin, which decreased the efficiency, but not the potency, of the effects of the two stimulatory agents on cyclic AMP accumulation.

Animals↗
PubMed1996

A light and electron microscopic study of GluR4-positive cells in human cerebral cortex.

In human cerebral cortex non-pyramidal neurons were densely labelled for the glutamate receptor subunit GluR4, but pyramidal cells only lightly. Some small glial cells were also positive. They were either 'non-activated', with thin processes, or 'activated', with thicker stem processes with irregular outlines due to the presence of surface projections, and containing phagocytosed neuronal debris. GluR4-positive glia are putatively identified as oligodendrocyte precursor-like cells, and have similar light microscopic features to NG2 chondroitin sulphate proteoglycan-positive cells [Levine, J.M.,J. Neurosci., 14 (1994) 4716-4730].

Adult↗
PubMed1995

Analysis of connectivity in the cat cerebral cortex.

The mammalian cerebral cortex is innervated by a large number of corticocortical connections. The number of connections makes it difficult to understand the organization of the cortical network. Nonetheless, conclusions about the organization of cortical systems drawn from examining connectional data have often been made in a speculative and informal manner, unsupported by any analytic treatment. Recently, progress has been made toward more systematic ways of extracting organizing principles from data on the network of connections between cortical areas of the monkey. In this article, we extend these approaches to the cortical systems of the cat. We collated information from the neuroanatomical literature about the corticocortical connections of the cat. This collation incorporated 1139 reported corticocortical connections between 65 cortical areas. We have previously used an optimization technique (Scannell and Young, 1993) to analyze this database in order to represent the connectional organization of cortical systems in the cat. Here, we report the connectional database and analyze it in a number of further ways. First, we employed rules from Felleman and Van Essen (1991) to investigate hierarchical relations among the areas. Second, we compared quantitatively the results of the optimization method with the results of the hierarchical method. Third, we examined quantitatively whether simple connection rules, which may reflect the development and evolution of the cortex, can account for the experimentally identified corticocortical connections in the database. The results showed, first, that hierarchical rules, when applied to the cat visual system, define a largely consistent hierarchy. Second, in both auditory and visual systems, the ordering of areas by hierarchical analysis and by optimization analysis was statistically significantly related. Hence, independent analyzes concur broadly in their ordering of areas in the cortical hierarchies. Third, the majority of corticocortical connections, and much of the pattern of connectivity, were accounted for by a simple "nearest-neighbor-or-next-door-but-one" connection rule, which may suggest one of the mechanisms by which the development of cortical connectivity is controlled.

Animals↗
PubMedDate not supplied

Analysis of connectivity: neural systems in the cerebral cortex.

The mammalian cerebral cortex is composed of many distinct areas, which are very richly interconnected. The very large number of connections between cortical areas require analysis to be undertaken before reliable conclusions about the organization of neural systems in the cortex can be drawn. We review the methodology and results of two means of analysing central nervous connectivity, hierarchical analysis and optimization analysis. We conclude that these methods are reliable methods for analysing neural connectivity data, and that their results concur. The analyses indicate that all major cortical sensory systems are organized hierarchically, some central sensory systems are divided structurally into several "streams" of processing, the cortical motor system is embedded in the cortical somatosensory system, the frontal and limbic structures are connectionally associated, and that these frontal and limbic areas are invariably associated with the least peripheral sensory processing regions, and are therefore connectionally central. Finally, we discuss the differences on this common plan between the organizations of the cat and primate that these analyses reveal.

Animals↗
PubMedDate not supplied

Patch-clamp studies of voltage-gated currents in identified neurons of the rat cerebral cortex.

In the cerebral cortex, neurons can be classified into 2 broad morphological classes, referred to as pyramidal and nonpyramidal (stellate) cells, which correspond to functional classes of projection neurons and local circuit interneurons, respectively. In this study, we demonstrate that specific morphological, immunohistochemical, and physiological features, that allow class distinction of neurons in situ, are retained in acutely isolated neocortical neurons. Furthermore, voltage-clamp analysis with patch-clamp techniques indicate the differences in functional properties in adult neurons, reflect cell-specific, developmental changes in the density and type of specific classes of Na+, K+ and Ca2+ channels expressed. The differences in channel properties contribute to the different input-output relations of neocortical neurons, which enable inhibitory neurons to follow excitatory inputs faithfully and projection neurons to have more integrative roles.

Action Potentials↗
PubMed2005

Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex.

The mammalian cerebral cortex comprises six layers of neurons. Cortical progenitors in the ventricular zone generate neurons specific to each layer through successive cell divisions. Neurons of layer VI are generated at an early stage, whereas later-born neurons occupy progressively upper layers. The underlying molecular mechanisms of neurogenesis, however, are relatively unknown. In this study, we devised a system where the Notch pathway was activated spatiotemporally in the cortex by in vivo electroporation and Cre-mediated DNA recombination. Electroporation at E13.5 transferred DNA to early progenitors that gave rise to neurons of both low and upper layers. Forced expression of a constitutively active form of Notch (caNotch) at E13.5 inhibited progenitors from generating neurons and kept progenitors as proliferating radial glial cells. After subsequent transfection at E15.5 of a Cre expression vector to remove caNotch, double-transfected cells, in which caNotch was excised, migrated into the cortical plate and differentiated into neurons specific to upper layers. Bromodeoxyuridine-labeling experiments showed that the neurons were born after Cre transfection. These results indicate that cortical progenitors that had been temporarily subjected to Notch activation at an early stage generated neurons at later stages, but that the generation of low-layer neurons was skipped. Moreover, the double-transfected cells gave rise to upper-layer neurons, even after their transplantation into the E13.5 brain, indicating that the developmental state of progenitors is not halted by caNotch activity.

Animals↗
PubMed1992

Synthesis and release of GABA in cerebral cortical neurons co-cultured with astrocytes from cerebral cortex or cerebellum.

Cerebral cortical neurons were co-cultured for up to 7 days with astrocytes after plating on top of a confluent layer of astrocytes cultured from either cerebral cortex or cerebellum (sandwich co-cultures). Neurons co-cultured with either cortical or cerebellar astrocytes showed a high stimulus coupled release of gamma-aminobutyric acid (GABA), which is the neurotransmitter of these neurons. When the astrocyte selective GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol was added during the release experiments, an increase in the stimulus coupled GABA release was seen, indicating that the astrocytes take up a large fraction of GABA released from the neurons. The activity of the GABA synthesizing enzyme glutamate decarboxylase, which is a specific marker of GABAergic neurons, was markedly increased in sandwich co-cultures of cortical neurons and cerebellar astrocytes compared to neurons cultured in the absence of astrocytes whereas in co-cultures with cortical astrocytes this increase was less pronounced. Pure astrocyte cultures did not show any detectable glutamate decarboxylase activity. The astrocyte specific marker enzyme glutamine synthetase (GS) was present at high activity in a glucocorticoid-inducible form in pure astrocytes as well as in co-cultures regardless of the regional origin of the astrocytes. When neurons were cultured on top of the astrocytes, the specific activity of GS was lower compared to astrocytes cultured alone, a result compatible with the notion that neurons are devoid of this enzyme. The results show that cortical neurons develop and differentiate when seeded on top of both homotypic and heterotypic astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Somatostatin release from rat cerebral cortex synaptosomes.

Rat cerebral cortex synaptosomes were exposed in superfusion to various depolarizing stimuli and the release of somatostatin-like immunoreactivity (SRIF-LI) was measured by means of a radioimmunoassay procedure. High KCl (9-50 mM) concentration dependently evoked SRIF-LI release; the evoked overflow reached a plateau at 25 mM KCl and was completely abolished when Ca2+ ions were omitted from the superfusion medium, independently of the concentration of KCl used. The 15 mM K(+)-evoked release of SRIF-LI increased sharply as the Ca2+ concentration was raised to 0.8 mM, then leveled off and reached a plateau at 1.2 mM. The 15 mM K(+)-evoked overflow, but not the spontaneous outflow, was partially decreased (50%) by 1 microM tetrodotoxin. The presence in the superfusion fluid of a mixture of peptidase inhibitors did not improve the recovery of SRIF-LI both in the absence and in the presence of high K+. Exposure of synaptosomes to veratrine (1-50 microM) induced release of SRIF-LI in a concentration-dependent way. The effect of the alkaloid was strictly Ca2+ and tetrodotoxin sensitive. Replacement of extracellular Na+ by sucrose caused an acceleration of the spontaneous SRIF-LI outflow that was inversely correlated to the Na+ content in the superfusion medium. The release evoked by the sodium-deprived media did not exhibit any calcium dependence. HPLC analysis of the samples collected during superfusion showed that greater than 90% of the SRIF-LI released either during the spontaneous outflow or by 15 mM KCl was represented by SRIF-14 (SRIF-28(14-28]. These values reflected the ratio SRIF-14/SRIF-28 found in synaptosomes at the end of the experiments.

Animals↗
PubMed1995

Tangential migration of neurons in the developing cerebral cortex.

The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299-302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434-440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.

Animals↗