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Ultrastructure of the yeast actin cytoskeleton and its association with the plasma membrane.

We characterized the yeast actin cytoskeleton at the ultrastructural level using immunoelectron microscopy. Anti-actin antibodies primarily labeled dense, patchlike cortical structures and cytoplasmic cables. This localization recapitulates results obtained with immunofluorescence light microscopy, but at much higher resolution. Immuno-EM double-labeling experiments were conducted with antibodies to actin together with antibodies to the actin binding proteins Abp1p and cofilin. As expected from immunofluorescence experiments, Abp1p, cofilin, and actin colocalized in immuno-EM to the dense patchlike structures but not to the cables. In this way, we can unambiguously identify the patches as the cortical actin cytoskeleton. The cortical actin patches were observed to be associated with the cell surface via an invagination of plasma membrane. This novel cortical cytoskeleton-plasma membrane interface appears to consist of a fingerlike invagination of plasma membrane around which actin filaments and actin binding proteins are organized. We propose a possible role for this unique cortical structure in wall growth and osmotic regulation.

Actins↗

[Developmental characteristics of the sensorimotor cortex of 7-8 days old rats in the roller cultures of free-floating brain slices].

Development and formation of neuronal architectonic of organotypic structures of sensomotor cortex of 7-8-day-old rats was studied in roller cultures. Free-floating cortical slices were cultured for 2-3 weeks. Serial paraffin sections of cultured tissue were stained with cresyl violet fast using Nissl's method. It was shown that during cultivation cortical slices changed their initial flat configuration and transformed into spherical bodies that retained main histiotypic features of cortical formations. Radially oriented pyramidal and fusiform neurons formed cortical structure that was not subdivided into individual layers and covered the whole surface of spherical tissue bodies. It is concluded that histogenetical processes were continuing in free-floating slices of sensomotor cortex of 7-8-day-old rats during roller cultivation. They result in formation of histiotypic cortical structure similar to phylogenetically more ancient allocortical formations of the forebrain.

Animals↗

Chronic ethanol consumption: from neuroadaptation to neurodegeneration.

In this review first we evaluate evidence on the role of the neurobiological alterations induced by chronic ethanol consumption in the development of ethanol tolerance, dependence and withdrawal. Secondly, we describe the neuropathological consequences of chronic ethanol on cognitive functions and on brain structures. Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. While tolerance mechanisms are unlikely to contribute to the neuroadaptive changes associated with ethanol dependence, it is otherwise clear that repeated high, intoxicating doses of ethanol trigger those neuroadaptive processes that lead to dependence and contribute to the manifestation of the abstinence syndrome upon withdrawal. An unbalance between inhibitory and excitatory neurotransmission is the most prominent neuroadaptive process induced by chronic ethanol consumption. Due to the diffuse glutamatergic innervation to all brain structures, the neuroadaptive alterations in excitatory neurotransmission can affect the function of most if not all of neurotransmitter systems. The expression of the withdrawal syndrome is the major causal factor for the onset and development of the neuropathological alterations. This suggests a link between the neuroadaptive mechanisms underlying the development of ethanol dependence and those underlying the functional and structural alterations induced by chronic ethanol. In animals and humans, specific alterations occur in the function and morphology of the diencephalon, medial temporal lobe structures, basal forebrain, frontal cortex and cerebellum, while other subcortical structures, such as the caudate nucleus, seem to be relatively spared. The neuropathological alterations in the function of mesencephalic and cortical structures are correlated with impairments in cognitive processes. In the brain of alcoholics, the prefrontal cortex and its subterritories seem particularly vulnerable to chronic ethanol, whether Korsakoff's syndrome is present or not. Due to the role of these cortical structures in cognitive functions and in the control of motivated behavior, functional alterations in this brain area may play an important role in the onset and development of alcoholism.

Acetylcholine↗

Integrating databases and expert systems for the analysis of brain structures: connections, similarities, and homologies.

The NeuroHomology Database system (NHDB) combines databases related to brain structures from different species with different knowledge management systems (KMSs) for systematization, evaluation and processing neurobiological data. Special attention is assessment of similarity of data from different species as a basis for exploring neural homologies. NHDB includes modules that handle brain structure and connectivity data, as well as inference engines for evaluation of the stored neurobiological information. The spatial inference engine evaluates the possible topological relations between cortical structures in different neuroanatomical atlases. The connectivity inference engine evaluates the reliability of information pertaining to fiber tracts as those are reflected in the literature. The inference engine for translation of neuroanatomical connections in different atlases evaluates the probability of existence of connections of interest in different parcellation schemes. Finally, the similarity inference engine calculates the overall degree of similarity of pairs of brain structures from different species by taking into account a set of eight criteria. We present examples of search for information in NHDB system, inferences of relations between cortical structures from equivalent neuroanatomical atlases, reconstruction of functional networks of brain structures from data collated from the literature, translation of connectivity matrices in equivalent parcellation schemes, and evaluations of similarities of brain structures from humans, macaques and rats.

Algorithms↗

Renin messenger RNA localization in congenital mesoblastic nephroma using in situ hybridization.

Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.

Female↗

[Interrelationship between the auditory, parietal and sensomotor regions of the dog cerebral cortex during a defensive conditioned reflex].

Interrelations between projection (auditory), associative (parietal) and integrative-triggering (sensorimotor) cortical areas were studied in dogs by EP parameters and localization during formation of defensive conditioned reflex to clicks. These interrelations were studied in intact animals and after ablation of either T3 areas or PI2 area of the auditory cortex. It was found that in intact animals auditory cortical areas are constantly involved in brain integrations whereas parietal ones show periodical participation (EPs in the parietal cortical area accompany some pairings of signal stimulus with reinforcement). Integrative-triggering cortical structures are involved in the systemic processes in the period of stabilisation of defensive reaction. After ablation of T3 area integrative-triggering cortical structures are turned on within a large exitation system from the beginning of the defensive reaction formation. After ablation of PI2 area parietal areas constantly participate in brain integrations. The nature of their participation in the forming of a given functional system is determined by the state of the auditory system or location of its injury.

Animals↗

Comparison of the fine structure of cortical and collicular terminals in the rat medial geniculate body.

Neurons throughout the rat medial geniculate body, including the dorsal and ventral divisions, display a variety of responses to auditory stimuli. To investigate possible structural determinants of this variability, measurements of axon terminal profile area and postsynaptic dendrite diameter were made on inferior colliculus and corticothalamic terminal profiles in the medial geniculate body identified by anterograde tracer labeling following injections into the inferior colliculus or cortex. Over 90% of the synapses observed were axodendritic, with few axosomatic synapses. Small (<0.5 microm(2)) and large (>1.0 microm(2)) collicular profiles were found throughout the medial geniculate, but were smaller on average in the dorsal division (0.49+/-0.49 microm(2)) than in the ventral division (0.70+/-0.64 microm(2)). Almost all corticothalamic profiles were small and ended on small-caliber dendrites (0.57+/-0.25 microm diameter) throughout the medial geniculate. A few very large (>2.0 microm(2)) corticothalamic profiles were found in the dorsal division and in the marginal zone of the medial geniculate. GABA immunostaining demonstrated the presence of GABAergic profiles arising from cells in the inferior colliculus. These profiles were compared with GABAergic profiles not labeled with anterograde tracer, which were presumed to be unlabeled inferior colliculus profiles or thalamic reticular nucleus profiles. The distributions of dendritic diameters postsynaptic to collicular, cortical and unlabeled GABAergic profiles were compared with dendritic diameters of intracellularly labeled medial geniculate neurons from rat brain slices. Our results demonstrate a corticothalamic projection to medial geniculate body that is similar to other sensory corticothalamic projections. However, the heterogeneous distributions of excitatory inferior collicular terminal sizes and postsynaptic dendritic diameters, along with the presence of a GABAergic inferior collicular projection to dendrites in the medial geniculate body, suggest a colliculogeniculate projection that is more complex than the ascending projections to other sensory thalamic nuclei. These findings may be useful in understanding some of the differences in the response characteristics of medial geniculate neurons in vivo.

Animals↗

A principle for the formation of the spatial structure of cortical feature maps.

Orientation-selective cells in the striate cortex of higher animals are organized as a hierarchical topographic map of two stimulus features: (i) position in visual space and (ii) orientation. We show that the observed structure of the topographic map can arise from a principle of continuous mapping. For the realization of this principle we use a mathematical model that can be interpreted as an adaptive process changing a set of synaptic weights, or synaptic connection strengths, between two layers of cells. The patterns of orientation preference and selectivity generated by the model are similar to the patterns seen in the visual cortex of macaque monkey and cat and correspond to a neural projection that maps a more than two-dimensional feature space onto a two-dimensional cortical surface under the constraint that shape and position of the receptive fields of the neurons very smoothly over the cortical surface.

Animals↗

[Use of the indicators of spectral power of cortical biopotentials for evaluation of the processes of generalization of epileptic activity].

Spatial density of spectral power of bioelectric cortical activity was analyzed in patients with primary-generalized (PG) and secondary-generalized (SG) epilepsy within a range of 0.5-30 Hz divided by 22 narrow bands. The range 0.5-7.0 Hz was shown to play a special role in epileptic activity generalization. The PG forms and SG epilepsy with a focus in the left hemisphere are characterized by the predominance of spatial density of spectral power in some bands of the low-frequency range in the cortical structures of the left hemisphere. On the contrary, SG epilepsy with a focus in the right hemisphere is marked by the same features in the cortical structures of the right hemisphere.

Action Potentials↗

Paleocortex is specified in mice in which dorsal telencephalic patterning is severely disrupted.

The patterning of the telencephalon is regulated by the concerted action of distinct mechanisms operating in different portions of this structure. Although much progress has been made in understanding the mechanisms underlying the specification of dorsal and ventral structures, little is known about the specification of the paleocortex, the olfactory cortex located at the interface of the dorsal and ventral telencephalon. The paleocortex is thought to be a dorsal, cortical structure, derived from the lateral extreme of the dorsal telencephalon. We examined mutant mice in which dorsal telencephalic patterning is severely disrupted, to ask how these perturbations affect the paleocortex. In the Lhx2-/- telencephalon, where the cortex is greatly shrunken such that medial and dorsal cortical tissue is undetectable, normal expression of several paleocortical markers is observed. The Gli3-/- telencephalon, where the dorsal telencephalon is ventralized, also displays paleocortical markers. In contrast, when the ventral telencephalon is almost completely deleted, such as in the BF1-/- brain, paleocortical markers are undetectable. These results indicate that the specification of the paleocortex can occur in spite of drastic perturbations of dorsal patterning. Furthermore, in the Lhx2 mutant, the paleocortex is juxtaposed to an expanded and mislocated source of Wnt and Bmp signaling, the cortical hem, whereas, in the Gli3 mutant, paleocortical markers arise even though the cortical hem is missing. This indicates that an increase or decrease in cues from this dorsal signaling center does not disrupt the specification of the paleocortex. Finally, by using an in vitro assay, we found that isolated explants of lateral telencephalon up-regulate normal expression of paleocortical markers when maintained in vitro, from as early as embryonic day (E) 10.5. Together, the results reveal that, although the paleocortex is considered to be a cortical structure, it is specified even when dorsal telencephalic patterning is grossly perturbed. Furthermore, our in vitro data reveal that, if mechanisms outside the lateral telencephalon are involved in the specification of the paleocortex, they must act extremely early, prior to E10.5.

Animals↗

[Changes in the structures of the cerebral cortex in experimental atherosclerosis with and without exposure to sound].

Albino rats fed an atherogenic diet for 3 months developed a marked depression of the anti-coagulation system of blood. The acoustic and sensomotor cortex showed dystrophic changes in the cortical structures, as well as signs of the reparative nature. Sound stimulation in the presence of atherosclerosis increased fibrinolytic activity and decreased heparin tolerance of blood plasma in animals sensitive to acoustic exposure and led to a greater severity and dissemination of dystrophic and destructive changes in the cortical structures, particularly in animals with convulsive seizures.

Animals↗

Impaired autoregulatory responses in contralateral kidneys of two-kidney, one-clip hypertensive rats.

1. Micropuncture and clearance experiments in two-kidney, one-clip renal vascular hypertensive rats examined the ability of the kidney contralateral to renal vascular stenosis to maintain renal function during conditions of reduced renal arterial blood pressure. 2. At their respective spontaneous blood pressures, renal vascular resistance was higher and glomerular filtration rate (GFR) and renal blood flow were not different in the contralateral kidneys of the hypertensive rats (170 +/- 5 mmHg) compared with normal animals (129 +/- 1 mmHg). Urine flow and absolute and fractional excretion of electrolyte were greater from the kidneys of the hypertensive animals. However, pressures in cortical structures were similar in the two groups. 3. As blood pressure was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in renal vascular resistance that failed to allow GFR, renal blood flow or pressures in cortical structures to be maintained. In contrast, normal rats efficiently autoregulated renal vascular resistance to allow GFR, renal blood flow and cortical pressures to be unchanged as blood pressure was altered between 130 and 115 mmHg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys; at comparable blood pressure these indices of excretory function were not different in the two groups. 4. These observations indicate that the contralateral kidney can maintain normal haemodynamic and glomerular function only at elevated blood pressure and suggest the possibility that the impaired capacity to autoregulate renal resistances may contribute to the maintenance of hypertension observed in this model.

Animals↗

Direct Evidence of Nociceptive Input to Human Anterior Cingulate Gyrus and Parasylvian Cortex.

Many lines of evidence implicate the anterior cingulate cortex (ACC, Brodmann's area 24) and parasylvian cortex in pain perception. Clinical studies demonstrate alterations in pain and temperature sensation after lesions of these structures. Imaging studies reveal increased blood flow in ACC and parasylvian cortex, both ipsilateral and contralateral to painful stimuli. Additionally, painful stimuli evoke potentials that seem to arise from these cortical structures. Short-duration cutaneous stimulation with a CO(2) laser evokes pain-related potentials (LEPs) with a vertex maximum and an initial negative peak followed by a positive wave. The cutaneous laser stimulus evokes a pure pain sensation due to selective activation of cutaneous nociceptors. Electrical source modeling has suggested that the vertex maximum of the scalp LEP arises, in part, from generators in the cingulate gyrus and parasylvian cortex. Thus, imaging and electrophysiologic studies suggest that these cortical structures are activated by painful stimuli. However, these studies incorporate multiple assumptions and therefore do not establish the presence of nociceptive inputs to ACC and parasylvian cortex. We review our recent reports of intracranial potentials evoked by painful stimuli. These studies provide direct evidence of nociceptive inputs to the human ACC and parasylvian cortex.

Journal Article↗

Multicatalytic proteinase is associated with characteristic oval structures in cortical Lewy bodies: an immunocytochemical study with light and electron microscopy.

The ATP-ubiquitin-dependent proteolytic pathway (ubiquitin pathway) is believed to be involved in the formation of various neuronal inclusion bodies including Lewy bodies (LBs), a pathological hallmark of Parkinson disease and diffuse Lewy body disease (DLBD). Since multicatalytic proteinase (MCP) is involved in the ubiquitin pathway, an investigation of whether MCP is involved in neuronal inclusion bodies would provide a clue to the mechanism underlying the formation of neuronal inclusion bodies as well as to the pathogenesis of degenerative neurological disorders. In this study, we investigated detailed immunolocalization of MCP in LBs in DLBD brains using light and electron microscopy. We raised three different monoclonal antibodies against purified human MCP. Each of them recognized different sets of MCP subunits on Western blotting. Immunohistochemically, anti-MCP antibodies recognized all ubiquitin-positive cortical LBs in situ as well as those isolated from frozen DLBD cortices, suggesting that MCP is present in LBs as a whole molecule exhibiting protease activity. In electron microscopy, MCP immunoreactivity (MCP-IR) was exclusively localized on a characteristic oval structure with an approximate diameter of 100 nm. This structure was distributed throughout the LBs and was devoid of ubiquitin immunoreactivity. Treatment of isolated LBs with 2% SDS, but not with 0.5% Triton X-100, removed this structure from LBs in which fibrous materials predominated. Ubiquitin immunoreactivity was also decreased in isolated LBs treated with 2% SDS, suggesting that the fibrous structures in LBs were not ubiquitinated in situ. Thus, it is suggested that LBs are subjected to a proteolytic process in which MCP plays a role via processing of specific components of LBs.

Aged↗

Autoradiographic localization of beta 1 and alpha 1-adrenoceptors in the midbrain and forebrain of normal and reeler mutant mice.

The distribution of alpha-1 and beta-1 adrenoceptors has been studied in the midbrain and forebrain of normal and reeler mutant mice, using autoradiographic visualization of radioiodinated HEAT and ICYP, respectively. All cortical structures and nuclear groups of the murine forebrain and midbrain bind ICYP and HEAT. For each ligand, there is substantial regional variation in binding density and these variations tend to observe boundaries between nuclei or cortical regions or the stratification of cortical regions. Regional variations in binding densities are generally different for ICYP and HEAT. Binding sites for ICYP are distributed densely throughout all fields of the neocortex (particularly, layers I-III greater than VI) and paleocortex, the striatum, pallidum, substantia nigra and superficial strata of the superior colliculus. Dense concentrations of binding sites for HEAT in cortical structures, by contrast, are limited to frontal (all layers except IV) and anterior cingulate regions of the neocortex and, as with ICYP, the stratum lacunosum-moleculaire of the regio superior of the hippocampal formation. In subcortical structures, again in contrast to the pattern with ICYP, binding density is greatest in the principal nuclei of the dorsal thalamus and the septal nuclei. The regional binding patterns of both ICYP and HEAT in the reeler brain are identical to those in the normal animal. Differential laminar binding patterns within the neocortex are approximately inverted in the two genotypes, however. Thus, binding of ICYP is densest in an inner zone of the mutant, but in the outer 3 layers of the normal neocortex. Binding of this ligand is of relatively lower density in an outer zone of the mutant and in the inner 3 layers of the normal neocortex. Similar inversions are characteristic of the laminar binding patterns of HEAT in the frontal, primary sensory and associational cortical regions of the two genotypes where densest binding is encountered superficially in reeler but at deeper levels of the normal neocortex.

Animals↗

PCO2 in renal cortex.

In a number of recent investigations a renal cortical PCO2 higher than that of systemic blood was reported. We have studied this problem with the use of micro-Severinghaus electrodes based on antimony, H+ liquid ion exchange, and glass pH electrodes with an inner buffer solution containing 0.5 mg/ml carbonic anhydrase (CA). Measurements in renal cortical structures (renal tubules, star vessels, capillaries, and glomeruli in Munich-Wistar rats) were compared with determinations in renal vein or artery performed with the same electrode in sequence. No significant differences in PCO2 were found between cortical structures and renal vein in control rats, in metabolic alkalosis, respiratory acidosis and alkalosis, and after CA inhibition. Nevertheless, absolute PCO2 levels, which followed the PCO2 of systemic blood, were markedly different in these groups. Measurements of pH and PCO2 at the same tubule site were compatible with HCO3- determinations in tubule fluid in vitro (made with use of the Henderson-Hasselbalch equation) in control rats. When proximal tubules were pump-perfused in vivo with a solution containing 30 mM NaHCO3, measured PCO2 approached that of the perfusing solution at high pump rates, and approached the free-flow value as rates were reduced to zero, indicating that the CO2 generated in the lumen equilibrated rapidly across the epithelium. Reducing renal blood flow by aortic clamping reduced renal cortical PCO2. In conclusion, in a large number of experimental conditions renal cortical PCO2 was never higher than that measured in systemic blood.

Animals↗

Effect of NMDA on the activity of cortical glutaminergic structures in delayed visual differentiation in monkeys.

The effect of intracortical perfusion with the glutamate agonist NMDA on visual recognition and short-term memory, as well as an on the responses of visual cortex neurons, were studied in rhesus macaques. A microdialysis technique was used in combination with multichannel microelectrode recording of single cortical cells in the immediate vicinity of the dialysis tube in a behavioral experiment in which the monkey had to solve a task involving delayed visual differentiation of stimuli of different colors. NMDA altered the characteristics of recognition in monkeys. The duration of information storage in short-term memory was increased significantly (2-4-fold), and there was a significant reduction in the motor response time for all delay periods. These changes were accompanied by a significant rearrangement of neuron activity in the visual cortex at all stages of the behavioral task. At different stages of the task, 70-85% of the neurons showed 2-5-fold increases in activity, while 6-20% showed reductions in activity. These results demonstrate an involvement of visual cortex glutaminergic structures in the process of visual recognition and short-term memory, as well as a nootropic effect obtained by intracortical administration of NMDA.

Action Potentials↗

Receptive field structure in cortical area 3b of the alert monkey.

More than 350 neurons with fingerpad receptive fields (RFs) were studied in cortical area 3b of three alert monkeys. Random dot patterns, which contain all stimulus patterns with equal probability, were scanned across these RFs at three velocities and eight directions to reveal the RFs' spatial and temporal structure. Area 3b RFs are characterized by three components: (1) a single, central excitatory region of short duration, (2) one or more inhibitory regions, also of short duration, that are adjacent to and nearly synchronous with the excitation, and (3) a region of inhibition that overlaps the excitation partially or totally and is temporally delayed with respect to the first two components. As a result of these properties, RF spatial structure depends on scanning direction but is virtually unaffected by changes in scanning velocity. This RF characterization, which is derived solely from responses to scanned random-dot patterns, predicts a neuron's responses to random patterns accurately, as expected, but it also predicts orientation sensitivity and preferred orientation measured with a scanned bar. Both orientation sensitivity and the ratio of coincident inhibition (number 2 above) to excitation are stronger in the supra- and infragranular layers than in layer IV.

Action Potentials↗