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Electrical self-stimulation of the mesencephalic central gray area: facilitation by lateral hypothalamic stimulation.

Three experiments were performed with BALB/c mice implanted both in the lateral hypothalamus (LH) and the dorsal part of the mesencephalic central gray area (CG). Initially, the effects of a brief electrical stimulation (0.2 sec) of the LH on approach and escape responses produced by continuous stimulation of the dorsal CG, were studied in a shuttle-box. Starting at an intensity of 10 microA, imposed LH stimulation both reduced approach latency and increased escape latency with CG stimulation. In the second and third experiments, the animals were placed in a standard self-stimulation (ICSS) box; depressions of a lever delivered brief electrical stimulations (0.2 sec). During the second experiment, it was observed that the very weak ICSS behavior produced by dorsal CG activation was greatly improved by forced LH stimulation. Finally, in the third experiment, simultaneous ICSS in LH and CG was compared with ICSS in LH alone. When low current intensities were used, simultaneous ICSS in LH and CG was more intense than ICSS in LH alone. These data especially suggest that dorsal CG stimulation has an appetitive component, and consequently that neuronal elements related to the positive reinforcement system are present in the dorsal CG area. Furthermore, the fact that one can obtain interactions between mesencephalic and hypothalamic ICSS is in accordance with the claim that the LH has connections with the CG area.

Animals↗

Cortical networks for visual reaching: intrinsic frontal lobe connectivity.

The anatomical substrates of reaching to visual targets were studied in monkeys (Macaca nemestrina) by combining behavioural neurophysiology and neuroanatomy. An instructed-delay reaching task was used to characterize the arm-related regions of the dorsolateral frontal cortex. This task revealed gradients of signal-, set- movement- and position-related activity along the rostrocaudal extent of the frontal lobe. The frontal mesial projections to these physiologically defined gradients were studied through anatomical methods based on the retrograde transport of distinguishable tracers. The tangential distribution of the cells of origin of these projections displayed a gradient-like arrangement similar to that defined physiologically in their terminal territory. These mesial projections to the dorsolateral frontal cortex may therefore be considered part of a cortical network wherein connections make only a limited contribution to the integration of different sources of information for the control of reaching movements. Further combination of such information must occur within each given cortical region by intrinsic local connections.

Animals↗

[Conditioned reflexes to time and effective stimuli after extirpation of the parietal region of the cortex in dogs].

Experiments on unrestrained dogs performed by the alimentary method showed that extirpation of the parietal cortex (field P) does not affect the previously elaborated and well stabilized conditioned reflexes to time, their reversal and temporal differentiation. The operated dogs retain their ability for relative perception of temporal intervals. Switching over of conditioned reflexes to time is disturbed. The conditioned reflexes to successive complex stimuli with simultaneous differentiation of their components are disturbed for a long time (up to seven months). Less disturbed are the conditioned reflexes to a simultaneous polysensory complex with parallel extinction of their components (within one month after the operation). An assumption has been made that the parietal zone of the cerebral cortex plays an important part in the mechanism providing for successive connections.

Animals↗

Topographic EEG analysis in two patients with basilar thrombosis.

The EEG activity of two patients with occlusion of the vertebral and basilar arteries was analyzed. Power maps, peak power frequency, and field power differences during both photic drive and verbal command were evaluated. Clinical findings of one patient fit the criteria of locked-in syndrome. Photic stimulation and event related desynchronization paradigm was used for testing the reactivity of EEG. Averaged EEG epochs during intended movement after verbal command showed significant alpha and sub-alpha power reduction. Regional differences of EEG reactivity were assumed secondary to the underlying hemispheric infarcts. Awareness of the patient in a locked-in state was documented by EEG analysis. In the second case permanent vegetative state was associated with a nonreactive rhythmic alpha pattern. Time sequence analysis of power ratios showed spontaneous alternating activity of alpha and sub-alpha generators. The authors conclude that pseudo-periodic fluctuation of alpha activity reflects partial preservation of thalamo-cortical connections.

Aged↗

Effects of intracavernous administration of adrenomedullin on erectile function in rats.

We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N(omega)-nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.

Adrenomedullin↗

Neural network model of the primary visual cortex: from functional architecture to lateral connectivity and back.

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene.

Action Potentials↗

Quantum correlations and secret bits.

It is shown that (i) all entangled states can be mapped by single-copy measurements into probability distributions containing secret correlations, and (ii) if a probability distribution obtained from a quantum state contains secret correlations, then this state has to be entangled. These results prove the existence of a two-way connection between secret and quantum correlations in the process of preparation. They also imply that either it is possible to map any bound entangled state into a distillable probability distribution or bipartite bound information exists.

Journal Article↗

An EEG-mapping study of "laughing": coherence and brain dominances.

The human expressive behavior termed laughter is triggered by pleasurable psychoemotional stimuli (Moody, 1978) and is possessed of a certain healing potential. According to split-brain studies (Sperry, 1966), psychoemotional stimuli are bound up with emotional activity in the right side of the brain. The idea thus suggests itself to study laughter generated by different sources with regard to the attendant electric brain activity between the right and left hemispheres. The present study was undertaken first with subjects in a state of normal consciousness and subsequently-given the possibility of increased affect stimulation in connection with laughter-under hypnosis. Having familiarized ourselves in our earlier work on brain dominances with the brain mapping EEG and having convinced ourselves of its greater efficiency in comparison with conventional EEG (Bick, 1985), we have had recourse to this method in the present study on approaches to the neurophysiological processes in the brain connected with laughter.

Brain↗

Evaluation of phase accuracy via topological and geometrical analysis of electron-density maps.

An empirical function is developed to measure the protein-like character of electron-density maps. The function is based upon a systematic analysis of numerous local and global map properties or descriptors. Local descriptors measure the occurrence throughout the unit cell of unique patterns on various defined templates, while global descriptors enumerate topological characteristics that define the connectivity and complexity of electron-density isosurfaces. We examine how these quantitative descriptors vary as error is introduced into the phase sets used to generate maps. Informative descriptors are combined in an optimal fashion to arrive at a predictive function. When the topological and geometrical analysis is applied to protein maps generated from phase sets with varying amounts of error, the function is able to estimate changes in average phase error with an accuracy of better than 10 degrees. Additionally, when used to monitor maps generated with experimental phases from different heavy-atom models, the analysis clearly distinguishes between the correct heavy-atom substructure solution and incorrect heavy-atom solutions. The function is also evaluated as a tool to monitor changes in map quality and phase error before and after density-modification procedures.

Electrons↗

Fluctuations in blood flow to acral skin in humans: connection with heart rate and blood pressure variability.

1. Spontaneous fluctuations in blood flow in arteries supplying acral skin were investigated with Doppler ultrasound in human subjects. Finger blood pressure, heart rate (HR) and cardiac output were measured simultaneously and noninvasively. 2. Synchronous fluctuations in flow were found in arteries supplying the hands and feet. The fluctuations were larger and more rapid than the flow variations which have been demonstrated with other methods. The magnitude of the total flow fluctuations in the hands and feet was estimated to be 5-10% of cardiac output in resting subjects. This range of flow fluctuations is made possible by spontaneous opening and closing of skin arteriovenous anastomoses (AVAs). 3. The fluctuations in skin blood flow were accompanied by inverse fluctuations in mean blood pressure (MAP). The power spectra of skin vascular conductance and MAP both contained maximum intensity at low frequencies, below 0.15 Hz, with high coherence. 4. The central circulatory events connected with the skin blood flow fluctuations were calculated from the experimental data with the use of transfer function analysis. There was a rise in HR, cardiac output and MAP starting 1-4 s before a cutaneous vasoconstriction. This indicates that the HR and MAP responses are not only passive effects of changes in peripheral resistance, but are the result of a simultaneous activation of the peripheral vascular and cardiac efferent branches of the autonomic nervous system. The HR and MAP responses are then modified, probably by baroreceptor activation.

Adult↗

Diffusion by extrinsic noise in the kicked Harper map.

A significantly improved analytic understanding of the extrinsically driven diffusion process is presented in a nonlinear dynamical system in which the phase space is divided into periodic two-dimensional tiles of regular motion, separated by a connected separatrix network (web) [previously studied by A. J. Lichtenberg and Blake P. Wood, Phys. Rev. Lett. 62, 2213 (1989)]. The system is represented by the usual "kicked Harper map" with added extrinsic noise terms. Three different diffusion regimes are found depending upon the strength of the extrinsic perturbation l relative to the web and regular motions. When the extrinsic noise is dominant over the intrinsic stochasticity and the regular rotation motions in the tile, diffusion obeys the random phase scaling l(2). When the extrinsic noise is dominant over the intrinsic stochasticity, but weaker than the regular rotation motion, the diffusion scales as lK(1/2), where K is the strength of the intrinsic kick. These findings agree well with numerical simulation results. When the extrinsic noise process is weaker than the stochastic web process, we analytically reproduce the well-known numerical result: The web diffusion is reduced by the ratio of phase-space areas of intrinsic to extrinsic stochasticity.

Journal Article↗

Saturating the eQTL map in Drosophila: Genome-wide patterns of cis and trans regulation of transcriptional variation in outbred populations.

Most genetic polymorphisms associated with complex traits are found in non-coding regions of the genome. Characterizing their effect presents a formidable challenge, and expression quantitative trait locus (eQTLs) mapping has been a key approach to do so. As comprehensive eQTL maps are available only for a few species, here we developed the Drosophila outbred synthetic population (Dros-OSP) and used it to characterize the landscape of transcriptional regulation in Drosophila melanogaster. We collected head and body transcriptomes and genomes from 1,286 outbred flies and mapped local and distant eQTLs for 98% of the genes. We characterized the network organization of the transcriptome across tissues and described the properties of local and distal eQTLs in terms of genetic diversity, heritability, connectivity, and pleiotropy. These results provide new insights into the genetic basis of transcriptional regulation in the fruit fly and offer a new mapping resource that will expand the possibilities currently available for the Drosophila community.

Animals↗

White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability.

The position and extent of individual fiber tracts within the white matter of human brains can be identified in vivo using diffusion tensor imaging (DTI) and fiber tracking methods. Previous to this study, however, the lack of three-dimensional (3-D) probability maps precluded comparing the anatomical precision of MRI studies with microscopically defined fiber tracts in human postmortem brains. The present study provides 3-D registered maps of the topography, course and intersubject variability of major fiber tracts, which were identified at microscopic resolution. The analyzed tracts include the corticospinal tract, optic and acoustic radiations, fornix, cingulum, corpus callosum, superior longitudinal, superior and inferior occipito-frontal and uncinate fascicles; sources and targets of fiber tracts include the lateral and medial geniculate nuclei and mamillary bodies. Tracts and nuclei were identified in serial myelin-stained histological sections of ten postmortem brains. The sections were 3-D reconstructed and registered to a standardized stereotaxic space of an in vivo MR reference brain by means of linear and non-linear, elastic transformations. The individual fiber tracts and nuclei were superimposed in the reference space, and probability maps were generated as a quantitative measure of intersubject variability for each voxel of the stereotaxic space. This study presents the first stereotaxic atlas of the course, location and extent of fiber tracts and related nuclei based on microscopically defined localization and topographic data taken at multiple levels on each of the three orthogonal planes. The maps are useful for evaluating and identifying fiber bundles in DTI, for localizing subcortical lesions visible in anatomical MR images and for studying neuronal connectivity.

Adult↗

Elucidating dynamic brain interactions with across-subjects correlational analyses of positron emission tomographic data: the functional connectivity of the amygdala and orbitofrontal cortex during olfactory tasks.

Covariance analyses of positron emission tomography (PET) data are used increasingly to elucidate the functional connectivity between brain regions during different cognitive tasks. Functional connectivity may be estimated by examining the covariance between regions over time or across subjects. In functional brain-mapping studies, across-subjects covariance matrices derived from within-task (nonsubtracted) and between-task (subtracted) data characterize different, complementary aspects of functional interactions. The authors study amygdala-orbitofrontal interactions during three task conditions (aversive olfaction, odor detection, and resting with eyes closed) to illustrate the strengths and limitations of across-subjects covariance analyses based on subtracted and nonsubtracted data. This example underscores the dynamic nature of connectivity between the amygdalae and orbitofrontal cortices and highlights the importance of including data from resting conditions in covariance analyses.

Adult↗

Lymphatic stomata in the murine diaphragmatic peritoneum: the timing of their appearance and a map of their distribution.

BACKGROUND: Fluid and free cells in the peritoneal cavity enter the lymphatics through the lymphatic stomata which are channels connecting the lymphatics in the peritoneal side of the diaphragm with the peritoneal cavity. While the stomata thus play a very important in the physiology of the peritoneal cavity, it is unclear when they appear or how they are distributed on the diaphragm. We therefore conducted an embryological study of the process and timing of mouse lymphatic stomata development in the peritoneal surface of the diaphragm. METHODS: The mouse diaphragm, at stage ranging from embryonic day 18 (ED18) to postnatal week 10 (PW10), was observed by scanning electron microscopy, and the number of lymphatic stomata was counted on each observation day. A map of the data was constructed to illustrate the process of appearance of lymphatic stomata. RESULTS: Lymphatic stomata were not found on ED18. They were first found on PD0 and their number increased exponentially until PW10. Lymphatic stomata were usually located in cuboidal cell areas but not in the areas lined with flattened cells. The cuboidal cell area with several lymphatic stomata was first found in the retroparasternal region on PD0, followed by in the muscular portion, as "ridges" on PD4 and "bands" on PD6 or up to a few days later. The long axis of the ridges and bands was oriented from the center to periphery of the diaphragm. Subsequently, cuboidal cell areas with lymphatic stomata formed along the border between the central tendon and the muscular portion, most frequently on PD10. Another cuboidal cell area with lymphatic stomata appeared rather suddenly ventral to the inferior vena cava on PD10. This was the full complement of cuboidal cell areas seen in the adult of PW10. CONCLUSION: These results verified that the course of the change of the shape and distribution of cuboidal cell areas parallels that of the underlying lymphatic lacunae, suggesting the delivery of some stimuli from the lymphatic lacunae to the overlying mesothelial cells that results in alternation of their cell shape.

Animals↗

Complete physical map of the Bacillus subtilis 168 chromosome constructed by a gene-directed mutagenesis method.

All the SfiI sites and most of the NotI sites were located precisely on the chromosome of Bacillus subtilis 168 by a novel method, termed gene-directed mutagenesis. The stepwise elimination of these restriction sites by this method allowed not only the physical connection of the restriction fragments but also the accurate determination of the position of the restriction sites themselves. The resulting physical map of the 4165 x 10(3) base-pair B. subtilis chromosome has been correlated with the genetic map by determination of the exact location of known genes. The complete physical map provides a rapid and accurate way for mapping of new genes as well as analysis of large DNA rearrangements on the chromosome. The novel strategy is, in principle, applicable to the analysis of the genome of other organisms.

Bacillus subtilis↗

New views of the thalamic reticular nucleus in the adult and the developing brain.

The thalamic reticular nucleus plays a crucial role in modifying the patterns of activity that can reach the cerebral cortex from the thalamus. Although the nucleus is generally viewed as a cell group with widespread and nonspecific thalamic and cortical connections, recent evidence has begun to stress the extent to which at least some of the reticular pathways transmit well-defined maps with a clear local sign from the cortex and the thalamus. Further, evidence from the adult structure of the nucleus and ongoing developmental studies suggest that the reticular nucleus plays an important part in organizing the earliest connections between cortex and thalamus and that the developmental sequence may explain the complex connections formed in the adult.

Aging↗

Gastrointestinal mucosal regeneration: role of growth factors.

Growth factors and their receptors play important roles in cell proliferation, migration, tissue injury repair and ulcer healing. In gastric mucosa, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) by activating their common receptor, control cell proliferation. TGF-alpha predominantly plays this role under normal conditions and after acute injury, while EGF exerts its actions mainly during healing of chronic ulcers. During regeneration of injured gastric mucosa, these growth factors serve predominantly to restore the epithelial component. Other growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) serve to promote restoration of the connective tissue and microvessels (angiogenesis) in injured mucosa. During healing of chronic ulcers, a new epithelial lineage secreting EGF and other growth peptides develops and the majority of cells lining the ulcer margin overexpress the EGF receptor. Activation of the EGF receptor induces dramatic increases in MAP (Erk -1 and -2) kinase activity and phosphorylation levels. Inhibition of this signaling pathway dramatically delays ulcer healing. Granulation connective tissue, which grows under the stimulation of bFGF and VEGF is the major source for regeneration of connective tissue lamina propria and microvessels within the ulcer scar. Other growth factors such as insulin - like growth factor, keratinocyte growth factor, hepatocyte growth factor and trefoil peptides have been implicated in gastrointestinal (gastric ulcers, colitis) regeneration following injury. This paper is intended to provide an overview of the role of growth factors in gastrointestinal mucosal regeneration.

Animals↗