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[Studies on behavioral and electrographic seizures and structural abnormalities using magnetic resonance image in chronic epilepsy model in rats--hippocampal-entorhinal-tempral neocortex neural pathway].

AIM AND METHODS: Repeated tetanus (60 Hz, 0.4-0.6 mA, 2 s) were delivered into the right and the left dorsal hippocampus (HPC), or into the right and the left medial temporal neocortex (MTNC) respectively to establish chronic temporal lobe epilepsy model in rats. The possible role of the HPC-Entorhinal cortex (EC)-MTNC-Neocortex neural pathway in epileptogenesis was discussed based on observing the abnormalities in behavior and in EEG or depth electrographes and in T2-weighted magnetic resonance images (T2-MRI). RESULTS: 1. Occurrence of primary, secondary WEDS and kindling effects were higher in the right dorsal HPC experimental group than those in other three experimental groups (P < 0.005, P < 0.001). T2-MRI signal hyperintensity was remarkable in lateral ventricles close to the HPC (P < 0.05), but not in the EC or in the MTNC. 2. These T2-MRI intensity increases were related to behavioral abnormalities in some MTNC-stimulated rats. 3. Asymmetric behavioral abnormalities and T2-MRI changes were observed in the left and the right DHPC-stimulated groups. CONCLUSION: HPC may be an "origin" for epileptogenesis and EC may play a "gating" role in it.

Animals↗

[The effect of peripheral stimulation on the electrical activity of the neocortex in chronic premesencephalic cats].

Chronic experiments were carried out with 19 adult cats. It is demonstrated that following a premesencephalic sectioning of the brain stem, with the lemniscal pathways being spared, on the second and third day after the surgery, auditory, olfactory and skin stimulations caused diffusive activation of the neocortex. Photic stimulation, though evoking responses in the visual cortex, was unable to desynchronize the neocortical electrical activity. Taking into account the data on the organization of hypothalamic afferent connections, it is suggested that diffuse activation of the neocortex in cats, when the mesencephalic reticular formation is completely excluded, occurs during auditory, olfactory and skin stimulations due to excitation of the posterior hypothalamus.

Animals↗

[Subtypes of muscarinic acetylcholine receptor following the experimental denervation of the cholinergic pathway ascending to the neocortex].

BACKGROUND: Use of an experimentally induced neurotoxic lesion of the ascending cholinergic pathway to the neocortex, in rat brain, to study the postulated selective loss of muscarinic receptor subtypes (mAChR) presynaptically located (autoreceptors). METHODS: Stereotaxic lesion of n. basalis magnocellularis was induced by 25 nmol Ibotenic acid injection in the right brain hemisphere of adult, male, Wistar rats. The contralateral hemisphere served as control. Antagonist (quinuclidinyl-benzilate) and agonist (carbachol) specific binding to mAChR receptors at equilibrium was studied 7 days post-lesion on a P2 fraction of brain cortex homogenate. Displacement of antagonist binding by carbachol was analyzed by "one-point" and "two-point" model fits. RESULTS: Muscarinic receptors on the control hemisphere show no sign of lesion related changes as compared to data for intact rat brain: Bmax = 0.896 pmol/mg protein and Kd = 0.25 nM. In the lesioned hemisphere a -10.3% loss of antagonist binding (not statistically significant) was observed, with an increase in receptor affinity. Heterogeneity of agonist binding was found; receptor subtype analysis showed that the proportion M2/M1 was unchanged but an increase in carbachol (M2 selective affinity) did appeared. CONCLUSIONS: We found no evidence of a selective presynaptic localization of muscarinic receptor sub-types on terminals of the cholinergic ascending pathway to the neocortex. A receptor loss related to the intensity of the neurotoxic lesion is suggested as well as the presence of regulative mechanisms (hypersensitivity) for receptors.

Afferent Pathways↗

Neuroblastoma grafts are noninvasively removed within mouse neocortex by selective laser activation of intracellular photolytic chromophore.

Studies of neural cell transplantation would be aided by the ability to damage or destroy, noninvasively and extremely selectively, grafted cells at defined times following their initial implantation. Mechanisms of graft integration and performance could be investigated, also providing insight into natural injury and repair mechanisms. At long wavelengths between 650 and 850 nm, laser energy can penetrate several millimeters of brain tissue without absorption or damage to the unpigmented tissue. However, targeted cells are selectively damaged by illumination at these long wavelengths if they contain latex nanospheres with incorporated cytolytic chromophores (e.g., chlorin e6). Light penetration allows many thousands of cells to be lesioned simultaneously, noninvasively, and deep within a surrounding matrix of other tissue. Such laser-activated damage has been termed laser photolysis (PL). We studied damage to C1300 neuroblastoma (NB) cells grafted into mouse neocortex in vivo by this process of PL. NB cells provided a simple and reproducible model of neural grafting, allowing direct histologic assessment of cellular growth and viability by distinct morphologic and mitotic criteria. Cells were cultured by standard methods, labeled in vitro by brief exposure to nanospheres containing chlorin e6, and grafted to sites within deep layers of mouse neocortex. Mice were exposed to transcranial, fractionated, unfocused pulses of 670-nm-wavelength energy totaling 90-120 J/cm2. We histologically assessed graft growth and cellular viability over a period from 2 d to 4 weeks, measured graft volumes quantitatively during the period of early rapid growth in controls (2 and 7 d), and generated 3-D reconstructions from serial sections to assist in visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Structural basis of developmental changes in the cytoarchitecture of human neocortex transplants].

Early stages in development of transplants of the embryonal anlages of the human neocortex into the brain of mature rats have been studied at light optic level. The main attention has been paid to processes of proliferation, migration and differentiation of cells. Increasing amount of cells in the transplants takes place only at the expense of neuroepithelium; its reorganization results in a peculiar rearrangement of cells with formation of so called rosellas with numerous mitotically dividing cells. Owing to this growth the differentiating cells migrate from the rosellas radially, unlike their layer-by-layer organization in the control. These deviations are probably dominant in the disturbance of cytoarchitectonic organization of cells in transplants of neocortex in mature mammalia.

Animals↗

Inhibition of norepinephrine and acetylcholine release from human neocortex by omega-conotoxin GVIA.

Superfused slices of human neocortex, prepared from surgically removed tissue (to gain access to subcortical tumors) and prelabeled selectively with [3H]norepinephrine (NE) or [3H]choline, were stimulated electrically to evoke tritium overflow. This tritium overflow was abolished by the sodium channel blocker tetrodotoxin and by withdrawal of extracellular Ca++. Thus, the action potential-induced, exocytotic tritium overflow supports the assumption of a quasiphysiological release of NE from noradrenergic and of acetylcholine (ACh) from cholinergic nerve terminals, respectively. In addition, the modulation of NE release by adrenoceptor ligands displayed the appropriate pharmacology of alpha-2 autoreceptors; ACh release was modulated by muscarinic ligands. Both NE and ACh release decreased with the age of the patients. The effects of drugs on NE and ACh release were not age-related. The peptide modulator of the N-type voltage sensitive Ca++ channel, omega-conotoxin GVIA, inhibited NE release with an IC50 of about 14 nM and ACh release with an IC50 of about 3 nM, whereas L-type modulators were ineffective. The binding of [125I]omega-conotoxin GVIA to human neocortical membranes was of high affinity (KD = 1.3 pM) to one site (nH = 0.97) of substantial density (maximum binding = 878 fmol/mg of protein); the binding of the L-type modulator [3H]isradipine to these membranes was also of high affinity (KD = 89 pM) to one site (nH = 1.03) of lesser density (maximum binding = 429 fmol/mg of protein). In conclusion, Ca++ entry through N-type Ca++ channels, rather then L-type Ca++ channels, predominates in subserving NE and ACh release from noradrenergic and cholinergic nerve terminals, respectively, of human neocortex.

Acetylcholine↗

The basic structure of the neocortex in insectivorous bats (Miniopterus sthreibersi and Pipistrellus pipistrellus). A Golgi study.

A Golgi study of the neocortex of Miniopterus sthreibersi and Pipistrellus pipistrellus revealed the presence of pyramidal cells distributed in an orderly fashion and many types of local-circuit neurons including small, medium-size and large multipolar cells with smooth dendrites and generalized axonal arborizations, double-bouquet neurons, chandelier cells, spiny stellate cells in midlevel of the cortex, sparsely spined multipolar neurons with ascending axons and horizontal cells of layer VI. In addition, extraverted neurons of layer II widely branching into the molecular layer and giant multipolar cells with very long and smooth dendrites embracing the whole cortical thickness distinguished the organization of the neocortex in these primitive species.

Animals↗

Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex.

In order to understand further the role of NGF in the development of NGF-sensitive basal forebrain neurons and their afferent connections to the hippocampus and neocortex, we have used monoclonal antibody 192 IgG to detect and localize NGF receptors immunocytochemically in the developing rat brain. NGF receptor immunoreactivity (NGF-RI) is first visible at embryonic day 13 (E 13) in the ventrolateral telencephalic wall and follows a caudal-to-rostral gradient in its initial appearance. NGF-RI neuronal number and neuropil staining undergo substantial increases before birth, and extensive dendritic growth and increases in perikaryal size continue during the first 3 weeks of postnatal life. This growth and cellular differentiation, however, is followed in the fourth postnatal week and later by an apparent decrease in dendritic arborization and 50% shrinkage in the size of perikarya. Initial NGF-RI fiber outgrowth from immature basal forebrain neurons directed toward appropriate target fields is observed as early as E 15. The formation of a laminar pattern by septal axons in the hippocampal terminal fields and invasion of NB afferents into the cortex occur postnatally over a protracted time. In the hippocampus, NGF-RI is initially diffusely distributed, and wide bands of immature granule and pyramidal cells are almost devoid of immunoreactive fibers; however, with maturity, septal axon terminals become concentrated in narrow zones closely associated with the cellular layers. In the neocortex, early-arriving basal forebrain afferents accumulate in the intermediate zone underneath the darkly immunoreactive subplate before they enter The cortex. Dense subplate and transiently present, radially aligned fiber staining completely disappear in later postnatal week and are gradually replaced by specific axonal and terminal staining associated with NB afferents. The expression of NGF receptor in the subplate zone at the time afferents arrive and its subsequent disappearance with the specific terminal formation suggest that NGF receptor and concomitant accumulation of NGF in the subplate may act as a temporary target for the early-arriving basal forebrain afferents; ingrowing afferents may then be guided by radially oriented NGF-RI fibers to proper synaptic sites.

Afferent Pathways↗

[Demonstration of Cajal-Retzius cells and their processes in the neocortex of newborn mice using horseradish peroxidase].

In newborn mouse neocortex, the so-called Cajal-Retzius cells (CRc), which are usually considered as neurons due to their polarity, located exclusively in the first cortical layer, were visualized using local application of horseradish peroxidase (HRP) on the neocortex followed by its tangential sectioning. Close to the application site, the exogenous enzyme, taken up by some of the CRc, was revealed with 3,3' diaminobenzidin (DAB) according to the Graham and Karnovsky technique. The brown reaction product was seen to fill almost completely some of these cells giving a "Golgi like" picture. They had a fusiform bipolar pericaryon and processes extending only into the first cortical layer. A single thick process whose length reached 300 to 400 microns, almost rectilinear and tapering progressively at its end was a dendrite which bore thin expansions reaching the cortical surface where they sometimes ramified between the endfeet of the radial glia. The dendrite sometimes showed symmetrical synapses with an afferent axon of unknown origin. The CRc axon was very thin (0.5 microns in diameter) and gave off at random numerous collaterals whose number and trajectories varied greatly from one cell to the other. The axonal processes could often be followed over a millimeter. They ended either abruptly because HRP had not diffused far enough into the process or terminated with large growth cones bearing numerous digitiform filopodia. The presence of growth cones thus suggested that the processes were exploring the cellular environment of the first cortical layer. In the newborn, CRcs appeared as still immature neurons.

Animals↗

[Effect of protein-energy deficiency on the composition of the glial population of the mouse neocortex].

A quantitative analysis of the cellular elements composition of the neocortex has been performed in 40-day-old mice, that have been given full-bodied synthetic diet (10% of protein) and the diet with the half concentration of the nutritive substances (5% of protein) beginning from the 10th day of their life. The protein-energetic insufficiency during the postnatal period produces retardation in the formation and differentiation processes of oligodendrogliocytes, as well as results in decrease of gliocytesatellites in the neocortex.

Animals↗

Physostigmine enhances blood flow-metabolism ratio in neocortex.

Inhibition of central nervous system cholinesterase with a single pulse of physostigmine induces a pronounced increase of blood flow in the neocortex, cingulate gyrus, claustrum, and amygdala. This phenomenon is not accompanied by an increase in energy metabolism and may help explain the effect of this drug on memory in normal humans and patients with Alzheimer's disease, as well as other conditions. In contrast, a parallel increase of blood flow and metabolism was observed in the superior colliculus, a component of the visual pathways. Prolonged administration of physostigmine lead to persistent vasodilatation in the neocortex, a lessening of this effect in cingulate gyrus, claustrum and amygdala, and an increase in primary olfactory cortex and hippocampus when compared with single pulse administration. Effects of physostigmine on glucose utilization remained essentially the same as with pulse administration.

Animals↗

[DNA repair in mammalian nerve cells. II. DNA synthesis in neurons, induced by gamma-irradiation of isolated rat neocortex slices].

DNA synthesis was studied in the neocortex neurons of 0-, 14- and 60-day old rats after gamma-irradiation in vitro of isolated slices of the neocortex on determining 3H-thymidine incorporation into DNA. Gamma-irradiation (20 Grays) increases levels of DNA synthesis for all the age groups of animals examined. The induced DNA synthesis in neurons of newborn rats is higher than that in 14- and 60-day old animals. Specificity of DNA synthesis in the process of nerve cell differentiation is discussed.

Aging↗

[Functional topography of afferent projections of the horizontal division of the nucleus of the diagonal band in the dorsolateral neocortex of the cat].

EPs recording under Nembutal anaesthesia during stimulation of the medial section of the horizontal part of the diagonal band nucleus (HNDB) shows a wide spreading of HNDB afferentation over the neocortex: from the frontal area to the medial and some posterior parts of the auditory, parietal areas and Ep zone, with the least activation of the latter three regions and activation increasing intensity correspondingly in the somatic zones II, I (SII, SI), motor and frontal cortex. Such reduction of signals flow intensity oriented both in caudal and ventral directions of the cortex goes with foci of maximal activity of these signals in the motor, parietal areas and zones of representation of various body parts in SI and SII. Traits of similarity and differences of signal's projections in the neocortex from HNDB and thalamic relay nuclei have been revealed. A hypothesis is substantiated on different mechanisms underlying peculiarities of influences of these subcortical nuclei on the cortex depending on the type of their afferent-neuronal links in the latter and their functional role in the brain activity.

Afferent Pathways↗

[Incorporation of neurons of transplants of embryonal rat neocortex in the achievement of sensory function of the cerebral cortex of the recipient].

The barrelfield of the adult rats was removed by suction and embryonic tissue of the somatosensory neocortex was transplanted into the cavity. Spontaneous and evoked activity of the grafted neurones was investigated extracellularly 2-3 months after the grafting. The light microscopy of the grafts revealed the presence of normal neuronal cells, but their distribution was diffuse, and they were not organized into barrels as in intact neocortex. The background activity of grafted neurones depended upon the level of the recipient's anaesthesia. The response types of the grafted neurones to vibrissae deflection and to tactile stimulation of the host body surfaces, their latencies and lability did not differ from such of the intact somatosensory cortex, but the receptive fields of the grafted neurones were larger. There was also substantial convergence of inputs from other surfaces upon the grafted neurones. The effectiveness of stimulation of the various skin areas was determined by the proximity of their neocortical representations to the graft.

Animals↗

Localization of glutaminase-like and aspartate aminotransferase-like immunoreactivity in neurons of cerebral neocortex.

The distribution of glutaminase (GLNase)- and aspartate aminotransferase (AATase)-immunoreactive cells was examined in the cerebral neocortex of rat and guinea pig and in the somatic sensorimotor and primary visual cortex of the Macaca fascicularis monkey. These enzymes are involved in the metabolism of glutamate and aspartate, two amino acids thought to be excitatory amino acid transmitters for cortical neurons. In each of the species examined a large percentage of layer V and VI pyramidal neurons have pronounced glutaminase-like immunoreactivity (GLNase IR). In contrast, neurons in layers I, II, and IV show little GLNase IR. Layer III in the rat and guinea pig contains only a few, densely labeled GLNase-like-immunoreactive (GLNase-Ir) pyramidal neurons, whereas in the monkey the number of GLNase-Ir cells in layer III varies between cytoarchitectonic fields. Area 3b of the primary somatic sensory cortex and area 17 (primary visual cortex) contain few GLNase-Ir cells in layer III. However, layer III contains moderate numbers of GLNase IR in cells in areas 3a, 1, 2, 5, and in the primary motor cortex. Within the motor cortex the largest pyramidal ("Betz") cells are not labeled. In marked contrast to the results with antibody to GLNase, antibody to AATase labels cells that appear nonpyramidal in form, and these cells are in all cortical layers in each of the species examined. This distribution is roughly similar throughout all areas of rodent neocortex, but in monkey visual cortex AATase-immunoreactive neurons are more numerous in layers II-III, IVc, and VI. When combined with the findings of other studies, our results suggest that GLNase IR marks pyramidal neurons that use an excitatory amino acid transmitter. Antibody to AATase appears to mark intrinsic cortical neurons. The AATase immunoreactivity of these cells could indicate that they use an excitatory amino acid transmitter. However, their form and distribution in cortex suggest that this antibody labels GABAergic neurons.

Animals↗

[Transplantation of embryonal anlagen of the human neocortex into the brain of the rat].

A possibility for transplanting anlages of human embryonal neocortex into mature rat brain has been studied. Light- and electron-microscopic investigations demonstrate that the embryonal tissue of the human neocortex implants into the cerebral grey and white substance of mature rats. In the grafts cellular elements proliferate and differentiate, neuropil is formed. These results open certain perspectives for modelling investigations on histogenesis of neural tissues and on studying possibilities for clinical use of grafts of the human embryonal brain.

Animals↗

[Structural organization of the cetacean neocortex].

As a result of investigation on architectonics of structural organization of the brain neocortex in dolphin, frontal, parietal, temporal and occipital regions, as well as certain fields were distinguished. Monotonous character and incomplete stratification of the neocortical lamina, lack of clear border line and similarity with interstitial formations demonstrate symbolic meaning of the word neocortex as it is applied to the cetacean brain. Therefore, the term preneocortex is suggested for the dolphin brain.

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Coupling between neurons of the developing rat neocortex.

We have estimated the prevalence of coupling between neurons of the rat neocortex during postnatal development. Single intracellular injections of the fluorescent dye Lucifer Yellow CH resulted in dye coupling among 70% of neurons from 1 to 4 days of age. Dye coupling dropped to 30 to 40% by 10 to 18 days and occurred in 20% of injected adult neurons. The number of neurons per dye-coupled aggregate also decreased. Whereas three to seven coupled neurons were common in cortex of 1 to 4 days, aggregates of more than two neurons were exceptionally rare in adults. The frequency of dye coupling did not vary systematically with cortical depth at any age. When chemical synaptic activity was blocked, most 4-day neurons exhibited short latency antidromically evoked depolarizations which were relatively insensitive to repetitive activation and membrane polarization. These depolarizations may represent electrotonically conducted spikes from coupled neurons. No such potentials were found in adult neurons. The results suggest that neuronal coupling is extensive in immature rat neocortex, but that coupling declines at a time just before the numbers of chemical synapses increase most rapidly.

Aging↗