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[The structural-functional characteristics of the rostral sections of the neocortex in Chiroptera].

Studies have been made on the connections of rostral neocortex in bats in order to reveal connections with the structures of the auditory sensory system the existence of which is indicated by evident specific responses to ultrasound in the form of synchronization reaction. It was shown that dorsolateral parts of the rostral neocortex receive topically organized projections from the thalamic nuclei VPL and VL. Connections with the auditory cortex and suprageniculate nucleus are not evident. Afferents of the medial wall of the rostral cortex originate from the thalamic nuclei MD and AM. Possible pathways of auditory afferentation to the dorso-lateral part of rostral neocortex are discussed.

Acoustic Stimulation↗

Relation of the insular claustrum to the neocortex in Insectivora.

The claustra of 9 species of Insectivora (Sorex araneus, Sorex minutus, Tenrec ecaudatus, Solenodon paradoxus, Neomys fodiens, Erinaceus europaeus, Talpa europaea, Desmana moschata, Potamogale velox) were investigated. In all examined animals we found two parts of the insular claustrum: the main part called by us the pars principalis and more medially situated lamina profunda claustri. In the "basal" Insectivora the main part is in close contact with the layer VIa of the neocortex. In some more developed "basal" and in all "progressive" Insectivora the area capsularis appears. Dorsolaterally it separates the main part of the insular claustrum from the neocortex and possesses, besides neurons, also numerous fibers of the extreme capsule. The above data strongly suggest that in the phylogenesis the insular claustrum originates from the cortex from which it gets separated by the extreme capsule. Lamina profunda claustri is rather a narrow band of neurons situated on the medial side of the pars principalis and mostly separated from it by a thin lamina of white substance. Lamina profunda is continuous with the layer VIb of the neocortex.

Animals↗

[The comparative characteristics of the neuronal activity in surviving slices of transplanted and intact neocortex].

The background single unit activity and single or multiunit responses to electrical stimulation of the rat's embryonic cortex, grafted into the somatosensory cortex of adult rats were investigated in a slice preparation. The same characteristics of the intact cortex neurons were observed as a control. The percentage of neurons with background activity within grafts was higher, than that within intact neocortex slices (23% and 6%, respectively). However the percentage of neurons responding to electrical stimulation of the recipient neocortex was lower in grafts. The mean latency of multiunit responses of graft neurons was longer, than that of neurons of the intact neocortex recorded at the same distance from the stimulating electrode (19.4 +/- 5.0 and 5.8 +/- 1.1 ms, respectively). Duration of the evoked population discharges was approximately ten times longer in grafts. It is concluded that there are local functional connections between a graft and the host brain and that inhibitory processes within grafts are weak. Functional integration of grafts with the host brain of the recipients after cranial trauma is shown.

Animals↗

[Cases of numerous diffuse plaques in the neocortex but without severe senile changes in the hippocampus].

Using modified Bielschowsky method, we studied neuropathologically 159 aged subjects autopsied during the period from 1976 to 1988, of which we found 19 cases (average age at death: 82.6 ys) with numerous diffuse plaques in the frontal and temporal neocortex and no severe senile changes in H1-H3 of Ammon's horn (dp group). Amyloid angiopathy had been excluded and one case was excluded because of considerable cerebrovascular lesions. The dp group was divided into 8 demented (average age at death: 86.0 ys) and 10 nondemented patients (average age at death: 79.7 ys). We compared the number, type, and ratio of types of senile plaques in the frontal cortex, temporal cortex, and putamen of the demented and nondemented groups, and obtained the following results: (1) Eight (14%) of the 59 nondemented and 8 (40%) of the 20 demented cases in which no severe senile changes in the neocortex and hippocampus had been detected by Bodian stain showed numerous diffuse plaques in the neocortex when the modified Bielschowsky method was used. (2) The ratio of classic and primitive plaques to diffuse plaques in the frontal cortex was the same in both groups, but the nondemented group had exclusively diffuse plaques in the temporal cortex. (3) In the putamen 2 nondemented cases (20%) and 6 demented cases (75%) had exclusively diffuse plaques. We considered that classic and primitive plaques are more closely related to dementia than are diffuse plaques in the temporal lobe in cases without severe senile changes in the hippocampus.

Aged↗

[Comparative analysis of the neocortex during the ontogenesis of cetaceae and primates].

Comparative ontogenetic investigation of cytoarchitectonics of the cerebral neocortex has been performed in Cetacea and Primates using paraffin frontal and sagittal cerebral sections stained after Nissl. Cerebral hemispheres of dolphins, whales, monkeys and human being have been studied at various periods of prenatal development and in mature individuals. The comparison has been made at similar stages of cytoarchitectonical differentiation of the cortical plate. At two first stages of the prenatal ontogenesis (formation of the cortical plate and its differentiation into layers) there is not any principle differences between the Cetacea and Primates. Peculiarities of the cerebral cortical plate differentiation in the Cetacea (absence of the internal granular layer IV) is determined at the stage of stratification. Similar agranular character of the cerebral cortex differentiation is maintained during the whole subsequent ontogenesis in the Cetacea (heterogenetic type of the neocortex after Brodman). Absence of the layer IV in the cerebral neocortex determines some other principles in the spatial organization of the cortical-subcortical and in the intracortical connections in the Cetacea brain. This is confirmed by modern data of morphological and electrophysiological investigations. Perhaps, a comparatively more simple initial architectonics of the Cetacea brain limited the level of their functional possibilities, the latter is comparable only with anthropoid apes.

Adaptation, Biological↗

[Effect of electric stimulation of the hippocampus and neocortex on limbic cortex neurons in the rabbit].

Extracellular recording of neuronal activity in anterior and posterior cingulate cortex was performed in unanaesthetized rabbits during electrical stimulation of the hippocampus and associative areas of anterior and posterior neocortex. Stimulation of the hippocampus was significantly more effective for posterior cingulate neurons (60% of reactive units) than for the anterior ones (18%). Most of reactive neurons in posterior cingulate cortex responded by time-locked effects; in anterior cingulate cortex such responses were rare. The latencies of the posterior cingular neuronal responses constituted two separate groups with the mean values 12.3 +/- 6.5 ms and 50.2 +/- 10.0 ms. Various forms of the activity suppression were also observed during hippocampal stimulation. Stimulation of posterior neocortex was almost equally effective for both areas of cingulate cortex: in more than a third of the units tested it evoked initial discharge followed by suppression of activity. Stimulation of anterior neocortex evoked such responses only in a limited proportion of anterior cingulate cortex neurons. The facts are discussed in the light of recent morphological data on connections between the investigated structures.

Animals↗

[Asymmetrical distribution of noradrenaline in the neocortex, hippocampus and adrenal glands of rats and changes with chronic activity restriction].

The norepinephrine content of neocortex, hippocampus, and adrenals of adult male Wistar rats was estimated. In normal rats an asymmetrical right-left-distribution of the norepinephrine content was found. Neocortex and hippocampus showed a contralateral, neocortex and adrenals an ipsilateral ratio. Chronic stress cancelled this right-left asymmetry of norepinephrine distribution. In brain the levelling appeared earlier than in adrenals.

Adrenal Glands↗

Comparison of brain structure volumes in Insectivora and Primates. I. Neocortex.

Based on volume measurements the total neocortex increases enormously from the lower ('basal') Insectivora, through prosimians, monkeys and apes up to man. In man it is about 132 times larger than in the average basal Insectivora of (theoretical) equal body weight and 232 times larger than in the insectivoran species which has the least developed neocortex. Within the neocortex the white matter increases more markedly than the grey matter. For man the white matter reaches a value 298 times that of the basal Insectivora and the grey matter reaches a value 198 times greater. Within the grey matter the cell dense layers (laminae 2-6) increase distinctly more than the molecular layer (lamina 1). Thus in man the volume of layers 2-6 is 272 times greater than that in basal Insectivora and the molecular layer is 68 times greater. When related to the total grey matter the percentage of the molecular layer clearly decreases from about 32% in the lower Insectivora to 12% in higher primates.

Animals↗

[Functional differentiation of different portions of the the rat neocortex].

The effect of uni- and bilateral ablation of rostral and caudal parts of neocortex on conditioned avoidance reflex was studied on naive and pretrained albino rats. Maximal impairment of the reflex was seen after bilateral ablation of the caudal region of neocortex, minimal one--after unilateral neocortex ablation. The rats without rostral cortex showed medium impairment. After extirpation of caudal cortex the number of positive reactions to light was greater in pretrained rats than in naive ones. After total cortical extirpation the previously elaborated conditioned reflex disappeared irreversibly. The conclusion is made on functional heterogeneity of the rostral and caudal cortex.

Animals↗

Effects of 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810) and some antiepileptics on the kindled seizures in the neocortex, hippocampus and amygdala in rats.

Effect of 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810) on kindled seizures in the neocortex, hippocampus and amygdala was studied in comparison with that of clinically proved antiepileptics, and the differences in kindled seizure development in the three areas were also studied. The amygdala more rapidly developed a generalized seizure (kindled seizure) than the hippocampus and the neocortex. Although more days of stimulation were needed, the neocortex also developed a kindled seizure similar to limbic kindled seizures. Phenobarbital, carbamazepine, dipropylacetate and diazepam showed a depressant effect on the neocortical kindled seizures. Phenytoin showed a depressant effect only when it was administered intravenously. Phenobarbital and carbamazepine depressed the hippocampal kindled seizures, while phenytoin and diazepam had little effect. Phenobarbital and diazepam caused marked depression on the amygdaloid kindled seizures, but the effect of phenytoin, carbamazepine and dipropylacetate on them was weak or negligible. AD-810 showed a depressant effect on neocortical and hippocampal kindled seizures, but not on amygdaloid ones. The profile of AD-810 is similar to that seen with carbamazepine.

Amygdala↗

Newly formed host cells in a grafted juvenile neocortex express neurone-specific marker proteins.

Recently we reported that a mouse foetal neural graft, when transferred into a lesioned juvenile neocortex, may induce cortical repair and stimulate proliferation of the host cells. The present study was focused on an immunohistochemical identification of neurones among these newly generated cells. Adjacent sections from the brains already used in our previous study were stained either with an antibody against the host-specific Thy-1 antigen, or with neurone-specific antibodies recognizing the microtubule-associated protein MAP2, the heavy subunit of neurofilaments and parvalbumin. Dividing cells, labelled repeatedly during the first three post-operative days with 3H-thymidine, were detected after 2 months by autoradiography. We found that in the repaired neocortical region newly formed host cells, whose distribution resembled the one found in an intact neocortex, also contained neurones. These new data corroborate our previous suggestion that a juvenile mammalian neocortex participates, after lesioning and under the presence of a foetal neural graft, in its own repair by the formation of new cells, including neurones.

Animals↗

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↗

Progesterone regulates gamma-aminobutyric acid B (GABAB) receptors in the neocortex of female rats.

After discovering that binding to GABAB receptors in rat neocortex varied as a function of the estrous cycle of the rat, we asked whether either or both of the major ovarian steroids could affect binding to GABAB receptors in the same way, namely, by regulating the apparent density (Bmax) of GABAB receptors. We report here that in ovariectomized rats, subcutaneous injection of progesterone alone, without the necessity of estrogen priming, increased the Bmax of baclofen binding to GABAB receptors in the neocortex. Radioimmunoassay of plasma progesterone before and after progesterone injections revealed that plasma progesterone levels similar to those reached during the progesterone surge in proestrus were associated with increased baclofen binding. The effect of progesterone upon baclofen binding was evident 4 h but not 1 h following progesterone treatment. There was some specificity with respect to the cortical receptors affected by progesterone in that under our conditions, progesterone did not increase agonist binding to 5-HT1A or GABAA receptors. We interpret our results to indicate that progesterone variation during the estrous cycle could be responsible for a component of the regulation of GABAB receptors that occurs in neocortex during the estrous cycle of the rat.

Adrenalectomy↗

5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex.

The influence of 5-HT receptor agonists on the expression of BDNF in brain was determined. Administration of a hallucinogenic 5-HT2A /2C receptor agonist, but not a 5-HT1A receptor agonist, resulted in a significant but differential regulation of BDNF mRNA levels in hippocampus and neocortex. In the hippocampus, the 5-HT2A /2C receptor agonist significantly decreased BDNF mRNA expression in the dentate gyrus granule cell layer but did not influence expression of the neurotrophin in the CA subfields. In parietal cortex and other neocortical areas, but not piriform cortex, the 5-HT2A /2C receptor agonist dramatically increased the expression of BDNF mRNA. The effect of the 5-HT2A /2C receptor agonist on BDNF mRNA in both the hippocampus and the neocortex was blocked by pretreatment with a selective 5-HT2A, but not 5-HT2C, receptor antagonist. The expression of BDNF mRNA in the hippocampus is reported to be decreased by stress, raising the possibility that the 5-HT2A receptor mediates this effect. Pretreatment with ketanserin, a 5-HT2A /2C receptor antagonist, significantly blocked the stress-induced downregulation of BDNF mRNA in hippocampus, in support of this hypothesis. The results of this study raise the possibility that regulation of BDNF expression by hallucinogenic 5-HT2A receptor agonists leads to adaptations of synaptic strength in the hippocampus and the neocortex that may mediate some of the acute and long-term behavioral effects of these agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Neocortex in the hippocampus: an anatomical and functional study of CA1 heterotopias after prenatal treatment with methylazoxymethanol in rats.

Migration disorders cause neurons to differentiate in an abnormal heterotopic position. Although significant insights have been gained into the etiology of these disorders, very little is known about the anatomy of heterotopias. We have studied heterotopic masses arising in the hippocampal CA1 region after prenatal treatment with methylazoxymethanol (MAM) in rats. Heterotopic cells were phenotypically similar to neocortical supragranular neurons and exhibited the same temporal profile of migration and neurogenesis. However, they did not express molecules characteristic of CA1 neurons such as the limbic-associated membrane protein. Horseradish peroxidase injections in heterotopia demonstrated labeled fibers not only in the neocortex and white matter but also in the CA1 stratum radiatum and stratum lacunosum. To study the pathophysiological consequences of this connectivity, we compared the effects of neocortical and limbic seizures on the expression of Fos protein and on cell death in MAM animals. After metrazol-induced seizures, Fos-positive cells were present in CA1 heterotopias, the only hippocampal region to be activated with the neocortex. By contrast, kainic acid-induced seizures caused a prominent delayed cell death in limbic regions and in CA1 heterotopias. Together, these results suggest that neocortical heterotopias in the CA1 region are integrated in both the hippocampal and neocortical circuitry.

Animals↗

Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic Alzheimer neocortex.

Long-term treatment by nonsteroidal anti-inflammatory drugs has been shown to decrease the incidence of Alzheimer's disease (AD). Both platelet-activating factor and interleukin-1beta, potent mediators of the inflammatory and immune response, strongly induce transcription of the cyclooxygenase-2 (COX-2) gene in brain cells. Using Northern and RT-PCR analysis, we have determined in 15 control and 10 sporadic AD human neocortical samples (age range, 60-82 yr; postmortem interval [PMI] range, 0.7-16.0 hr) the levels of COX-2 RNA in relation to the constitutively expressed COX-1 and beta-actin RNA message levels. Our results indicate that in short PMI brain, COX-1 and COX-2 transcripts are relatively low abundance RNA messages, ranging from a mean of 6.8% of the beta-actin signal in controls to 8.5% of the beta-actin signal in AD-affected brain. A large variation in the signal intensity for COX-2 RNA was noted in both control and AD; although there was a trend for higher COX-2 RNA message abundance in AD neocortex to +11.5% of that of controls, it did not reach statistical significance (ANOVA = 0.45). Several human tissues, including heart, skeletal muscle, lung, kidney, and spinal cord, displayed 4.6- and 2.8-kb COX-2 RNA message isoforms; however, the 4.6-kb COX-2 RNA predominated in the hippocampus and association neocortex. COX-2 RNA message was found to be degraded at similar rates in both control and AD tissues, and a strong positive correlation between the PMI and the intensity of the COX-2 RNA signal was noted (ANOVA = 0.006). Linear regression analysis indicated that the 4.6-kb COX-2 RNA is an unstable short-lived RNA species with a half-life of not more than 3.5 hr, a feature characteristic of immediate early gene transcripts. Individual hypervariability in COX-2 RNA message abundance may reflect various degrees of expression of AD-related inflammatory processes.

Aged↗

Computational principles of learning in the neocortex and hippocampus.

We present an overview of our computational approach towards understanding the different contributions of the neocortex and hippocampus in learning and memory. The approach is based on a set of principles derived from converging biological, psychological, and computational constraints. The most central principles are that the neocortex employs a slow learning rate and overlapping distributed representations to extract the general statistical structure of the environment, while the hippocampus learns rapidly, using separated representations to encode the details of specific events while suffering minimal interference. Additional principles concern the nature of learning (error-driven and Hebbian), and recall of information via pattern completion. We summarize the results of applying these principles to a wide range of phenomena in conditioning, habituation, contextual learning, recognition memory, recall, and retrograde amnesia, and we point to directions of current development.

Hippocampus↗

Proliferation and apoptosis in the developing human neocortex.

The cell kinetics of the developing central nervous system (CNS) is determined by both proliferation and apoptosis. In the human neocortex at week 6 of gestation, proliferation is confined to the ventricular zone, where mitotic figures and nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA) are detectable. Cell division is symmetric, with both daughter cells reentering mitosis. At week 7, the subventricular zone, a secondary proliferative zone, appears. It mainly gives rise to local circuit neurons and glial cells. Around week 12, the ventricular and subventricular zones are thickest, and the nuclear PCNA label is strongest, indicating that proliferation peaks at this stage. Thereafter, asymmetric division becomes the predominant mode of proliferation, with one daughter cell reentering mitosis and the other one migrating out. Towards late gestation, the ventricular and subventricular zones almost completely disappear and proliferation shifts towards the intermediate and subplate zones, where mainly glial cells are generated. A remnant of the subventricular zone with proliferative activity persists into adulthood. In general, proliferation follows a latero-medial gradient in the neocortex lasting longer in its lateral parts. Apoptotic nuclei have been detected around week 5, occurring in low numbers in the ventricular zone at this stage. Apoptotic cell death increases around midgestation and then spreads throughout all cortical layers, with most dying cells located in the ventricular and subventricular zones. This spatial distribution of apoptosis extends into late gestation. During the early postnatal period, most apoptotic cells are still located in the subcortical layers. During early embryonic development, proliferation and apoptosis are closely related, and are probably regulated by common regulators. In the late fetal and early postnatal periods, when proliferation has considerably declined in all cortical layers, apoptosis may occur in neurons whose sprouting axons do not find their targets.

Apoptosis↗