DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2008
Jennifer Brockhausen
Abstract Fluorescence resonance energy transfer (FRET) experiments at neuromuscular junctions in the mouse tibialis anterior muscle show that postsynaptic acetylcholine receptors (AChRs) become more tightly packed during the first month of postnatal development. Here, we report that the packing of AChRs into postsynaptic aggregates was reduced in 4-week postnatal mice that had reduced amounts of the AChR-associated protein, rapsyn, in the postsynaptic membrane (rapsyn+/, mice). We hypothesize that nerve-derived agrin increases postsynaptic expression and targeting of rapsyn, which then drives the developmental increase in AChR packing. Neural agrin treatment elevated the expression of rapsyn in C2 myotubes by a mechanism that involved slowing of rapsyn protein degradation. Similarly, exposure of synapses in postnatal muscle to exogenous agrin increased rapsyn protein levels and elevated the intensity of anti-rapsyn immunofluorescence, relative to AChR, in the postsynaptic membrane. This increase in the rapsyn-to-AChR immunofluorescence ratio was associated with tighter postsynaptic AChR packing and slowed AChR turnover. Acute blockade of synaptic AChRs with ,-bungarotoxin lowered the rapsyn-to-AChR immunofluorescence ratio, suggesting that AChR signaling also helps regulate the assembly of extra rapsyn in the postsynaptic membrane. The results suggest that at the postnatal neuromuscular synapse agrin signaling elevates the expression and targeting of rapsyn to the postsynaptic membrane, thereby packing more AChRs into stable, functionally-important AChR aggregates. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source]

Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system

JOURNAL OF NEUROCHEMISTRY, Issue 3 2006
Steve Poirier
Abstract Neural apoptosis-regulated convertase-1/proprotein convertase subtilisin-kexin like-9 (NARC-1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low-density lipoprotein receptor (LDLR) and possibly in neural development. Herein, we investigated the potential involvement of this proteinase in the development of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as models. Time course quantitative RT,PCR analyses were performed following retinoic acid (RA)-induced neuroectodermal differentiation of P19 cells. Accordingly, the mRNA levels of NARC-1/PCSK9 peaked at day 2 of differentiation and fell off thereafter. In contrast, the expression of the proprotein convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively. This pattern was not affected by the cholesterogenic transcription factor sterol regulatory element-binding protein-2, which normally up-regulates NARC-1/PCSK9 mRNA levels in liver. Furthermore, in P19 cells, RA treatment did not affect the protein level of the endogenous LDLR. This agrees with the unique expression pattern of NARC-1/PCSK9 in the rodent CNS, including the cerebellum, where the LDLR is not significantly expressed. Whole-mount in situ hybridization revealed that the pattern of expression of zebrafish NARC-1/PCSK9 is similar to that of mouse both in the CNS and periphery. Specific knockdown of zebrafish NARC-1/PCSK9 mRNA resulted in a general disorganization of cerebellar neurons and loss of hindbrain,midbrain boundaries, leading to embryonic death at ,,96 h after fertilization. These data support a novel role for NARC-1/PCSK9 in CNS development, distinct from that in cholesterogenic organs such as liver. [source]

Genetic and Developmental Modulation of Cardiac Deficits in Prenatal Alcohol Exposure

ALCOHOLISM, Issue 1 2000
Maria Fernanda Cavieres
Background: Increasing evidence demonstrates that genetic background is an important modulator of alcohol's effects on the developing fetus. Such effects are separable from maternal ethanol metabolism. Here, we study ethanol's effects on cardiogenesis in an avian model that shows strong cell death within neuronal and neural crest precursors following ethanol exposure. Methods: The study design tested the hypothesis that ethanol-induced losses of cardiac neural crest populations would disrupt outflow tract development and thus contribute to the valvuloseptal deficits observed in prenatal alcohol exposure. Three chick strains were exposed to alcohol at gestational windows between gastrulation and early heart septation (day 3 incubation), and then hearts were examined at the completion of morphogenesis (day 10 incubation). Results: Ethanol's impact on cardiac development was influenced by fetal genetics. The B300 X Hampshire Red cross exhibited pronounced cell death within cardiac neural crest populations but had normal development of the heart and aortic arches. Neural crest migration and differentiation into the distal outflow tract were also normal in these embryos, which suggested a capacity to repair earlier losses. The DeKalb White X Hampshire Red cross also did not exhibit cardiac defects. Hearts of the B300 strain had a unique phenotype with respect to ethanol exposure and exhibited a thin ventricular compact layer, dilatation, and reduced myosin/deoxyribonucleic acid and myosin/protein content, a phenotype that indicates disrupted myocardial maturation and inductive cues. The deficit was only observed when ethanol exposure occurred at stages 15 or 18 and apparently was independent of neural crest cell death. Such ventricular thinning might go undetected in the absence of extensive screening. Conclusions: Results add to the increasing evidence that genetic background strongly modulates the effects of prenatal alcohol exposure. The results also suggest that embryos have a varying capacity to repair and recover from earlier neural crest losses. [source]

Oral pathology in untreated coelic disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2007
G. CAMPISI
Summary Background Many coeliac disease patients with atypical symptoms remain undiagnosed. Aim To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis. Patients and methods One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed. Results Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427,4.926) and soft tissue lesions (OR = 41.667, CI = 18.868,90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis. Conclusions The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low. [source]

Neural and orofacial defects in Folbp1 knockout mice ,

BIRTH DEFECTS RESEARCH, Issue 4 2003
Louisa S. Tang
Abstract BACKGROUND Folic acid is essential for the development of the nervous system and other associated structures. Mice deficient in the folic acid-binding protein one (Folbp1) gene display multiple developmental abnormalities, including neural and craniofacial defects. To better understand potential interactions between Folbp1 gene and selected genes involved in neural and craniofacial morphogenesis, we evaluated the expression patterns of a panel of crucial differentiation markers (Pax-3, En-2, Hox-a1, Shh, Bmp-4, Wnt-1, and Pax-1). METHODS Folbp1 mice were supplemented with low dosages of folinic acid to rescue nullizygotes from dying in utero before gestational day 10. The gene marker analyses were carried out by in situ hybridization. RESULTS In nullizygote embryos with open cranial neural tube defects, the downregulation of Pax-3 and En-2 in the impaired midbrain, along with an observed upregulation of the ventralizing marker Shh in the expanded floor plate, suggested an important regulatory interaction among these three genes. Moreover, the nullizygotes also exhibit craniofacial abnormalities, such as cleft lip and palate. Pax-3 signals in the impaired medial nasal primordia were significantly increased, whereas Pax-1 showed no expression in the undeveloped lateral nasal processes. Although Shh was downregulated, Bmp-4 was strongly expressed in the medial and lateral nasal processes, highlighting the antagonistic activities of these molecules. CONCLUSIONS Impairment of Folbp1 gene function adversely impacts the expression of several critical signaling molecules. Mis-expression of these molecules, perhaps mediated by Shh, may potentially contribute to the observed failure of neural tube closure and the development of craniofacial defects in the mutant mice. Birth Defects Research (Part A) 67:209,218, 2003. © 2003 Wiley-Liss, Inc. [source]

Neurophysiology of hunger and satiety

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008
Pauline M. Smith
Abstract Hunger is defined as a strong desire or need for food while satiety is the condition of being full or gratified. The maintenance of energy homeostasis requires a balance between energy intake and energy expenditure. The regulation of food intake is a complex behavior. It requires discrete nuclei within the central nervous system (CNS) to detect signals from the periphery regarding metabolic status, process and integrate this information in a coordinated manner and to provide appropriate responses to ensure that the individual does not enter a state of positive or negative energy balance. This review of hunger and satiety will examine the CNS circuitries involved in the control of energy homeostasis as well as signals from the periphery, both hormonal and neural, that convey pertinent information regarding short-term and long-term energy status of the individual. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:96,104. [source]

Neuro-mesodermal patterns in artificially deformed embryonic explants: A role for mechano-geometry in tissue differentiation

DEVELOPMENTAL DYNAMICS, Issue 3 2010
E.S. Kornikova
Abstract The mutual arrangement of neural and mesodermal rudiments in artificially bent double explants of Xenopus laevis suprablastoporal areas was compared with that of intact explants. While some of the bent explants straightened or became spherical, most retained and actively reinforced the imposed curvature, creating folds on their concave sides and expanding convex surfaces. In the intact explants, the arrangement of neural and mesodermal rudiments exhibited a distinct antero-posterior polarity, with some variability. In the bent explants, this polarity was lost: the neural rudiments were shifted towards concave while the mesodermal tissues moved towards the convex side, embracing the neural rudiments in a horseshoe-shaped manner. We associate these drastic changes in neuro-mesodermal patterning with the active extension and contraction of the convex and concave sides, respectively, triggered by the imposed deformations. We speculate that similar events are responsible for the establishment of neuro-mesodermal patterns during normal development. Developmental Dynamics 239:885,896, 2010. © 2010 Wiley-Liss, Inc. [source]

Role of VEGF and tissue hypoxia in patterning of neural and vascular cells recruited to the embryonic heart

DEVELOPMENTAL DYNAMICS, Issue 11 2009
Hongbin Liu
Abstract We hypothesized that oxygen gradients and hypoxia-responsive signaling may play a role in the patterning of neural or vascular cells recruited to the developing heart. Endothelial progenitor and neural cells are recruited to and form branched structures adjacent to the relatively hypoxic outflow tract (OFT) myocardium from stages 27,32 (ED6.5,7.5) of chick development. As determined by whole mount confocal microscopy, the neural and vascular structures were not anatomically associated. Adenoviral delivery of a VEGF trap dramatically affected the remodeling of the vascular plexus into a coronary tree while neuronal branching was normal. Both neuronal and vascular branching was diminished in the hearts of embryos incubated under hyperoxic conditions. Quantitative analysis of the vascular defects using our recently developed VESGEN program demonstrated reduced small vessel branching and increased vessel diameters. We propose that vascular and neural patterning in the developing heart share dependence on tissue oxygen gradients but are not interdependent. Developmental Dynamics 238:2760,2769, 2009. © 2009 Wiley-Liss, Inc. [source]

Transcriptional control of Rohon-Beard sensory neuron development at the neural plate border

DEVELOPMENTAL DYNAMICS, Issue 4 2009
Christy Cortez Rossi
Abstract Rohon-Beard (RB) mechanosensory neurons are among the first sensory neurons to develop, and the process by which they adopt their fate is not completely understood. RBs form at the neural plate border (NPB), the junction between neural and epidermal ectoderm, and require the transcription factor prdm1a. Here, we show that prior to RB differentiation, prdm1a overlaps extensively with the epidermal marker dlx3b but shows little overlap with the neuroectodermal markers sox3 and sox19a. Birthdating analysis reveals that the majority of RBs are born during gastrulation in zebrafish, suggesting that it is during this period that RBs become specified. Expression analysis in prdm1a and neurogenin1 mutant and dlx3b/dlx4b morpholino-injected embryos suggests that prdm1a is upstream of dlx3b, dlx4b, and neurogenin1 at the NPB. mRNA for neurogenin1 or dlx3b/dlx4b can rescue the lack of RBs in prdm1a mutants. Based on these data, we suggest a preliminary gene regulatory network for RB development. Developmental Dynamics 238:931,943, 2009. © 2009 Wiley-Liss, Inc. [source]

Ventral otic cell lines as developmental models of auditory epithelial and neural precursors

DEVELOPMENTAL DYNAMICS, Issue 4 2004
G. Lawoko-Kerali
Abstract Conditionally immortal cell lines were established from the ventral otocyst of the Immortomouse at embryonic day 10.5 and selected to represent precursors of auditory sensory neural and epithelial cells. Selection was based upon dissection, tissue-specific markers, and expression of the transcription factor GATA3. Two cell lines expressed GATA3 but possessed intrinsically different genetic programs under differentiating conditions. US/VOT-E36 represented epithelial progenitors with potential to differentiate into sensory and nonsensory epithelial cells. US/VOT-N33 represented migrating neuroblasts. Under differentiating conditions in vitro the cell lines expressed very different gene expression profiles. Expression of several cell- and tissue-specific markers, including the transcription factors Pax2, GATA3, and NeuroD, differed between the cell lines in a pattern consistent with that observed between their counterparts in vivo. We suggest that these and other conditionally immortal cell lines can be used to study transient events in development against different backgrounds of cell competence. Developmental Dynamics 231:801,814, 2004. © 2004 Wiley-Liss, Inc. [source]

Characterization of the plasticity-related gene, Arc, in the frog brain

DEVELOPMENTAL NEUROBIOLOGY, Issue 12 2010
Lisa A. Mangiamele
Abstract In mammals, expression of the immediate early gene Arc/Arg3.1 in the brain is induced by exposure to novel environments, reception of sensory stimuli, and production of learned behaviors, suggesting a potentially important role in neural and behavioral plasticity. To date, Arc has only been characterized in a few species of mammals and birds, which limits our ability to understand its role in modifying behavior. To begin to address this gap, we identified Arc in two frog species, Xenopus tropicalis and Physalaemus pustulosus, and characterized its expression in the brain of P. pustulosus. We found that the predicted protein for frog Arc shared 60% sequence similarity with Arc in other vertebrates, and we observed high Arc expression in the forebrain, but not the midbrain or hindbrain, of female túngara frogs sacrificed at breeding ponds. We also examined the time-course of Arc induction in the medial pallium, the homologue of the mammalian hippocampus, in response to a recording of a P. pustulosus mating chorus and found that accumulation of Arc mRNA peaked 0.75 h following stimulus onset. We found that the mating chorus also induced Arc expression in the lateral and ventral pallia and the medial septum, but not in the striatum, hypothalamus, or auditory midbrain. Finally, we examined acoustically induced Arc expression in response to different types of mating calls and found that Arc expression levels in the pallium and septum did not vary with the biological relevance or acoustic complexity of the signal. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 813,825, 2010 [source]

Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse elimination

DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2009
Rachel M. Sherrard
Abstract Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3-7, when CF-PC innervation changes from synapse formation to selective synapse elimination, and in a denervation-reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF-PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full-length and activated phosphorylated TrkB (phospho-TrkB) decreased from P4-5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF-PC reinnervation: in the denervated hemicerebellum phospho-TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF-PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]

Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats

DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2007
Mark D. Spritzer
Abstract Past research suggested that androgens may play a role in the regulation of adult neurogenesis within the dentate gyrus. We tested this hypothesis by manipulating androgen levels in male rats. Castrated or sham castrated male rats were injected with 5-Bromo-2,deoxyuridine (BrdU). BrdU-labeled cells in the dentate gryus were visualized and phenotyped (neural or glial) using immunohistochemistry. Castrated males showed a significant decrease in 30-day cell survival within the dentate gyrus but there was no significant change in cell proliferation relative to control males, indicating that androgens positively affect cell survival, but not cell proliferation. To examine the role of testosterone on hippocampal cell survival, males were injected with testosterone s.c. for 30 days starting the day after BrdU injection. Higher doses (0.5 and 1.0 mg/kg) but not a lower dose (0.25 mg/kg) of testosterone resulted in a significant increase in neurogenesis relative to controls. We next tested the role of testosterone's two major metabolites, dihydrotestosterone (DHT), and estradiol, upon neurogenesis. Thirty days of injections of DHT (0.25 and 0.50 mg/kg) but not estradiol (0.010 and 0.020 mg/kg) resulted in a significant increase in hippocampal neurogenesis. These results suggest that testosterone enhances hippocampal neurogenesis via increased cell survival in the dentate gyrus through an androgen-dependent mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source]

Seasonal plasticity of brain aromatase mRNA expression in glia: Divergence across sex and vocal phenotypes

DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2005
Paul M. Forlano
Abstract Although teleost fishes have the highest levels of brain aromatase (estrogen synthase) compared to other vertebrates, little is known of its regulation and function in specific brain areas. Previously, we characterized the distribution of aromatase in the brain of midshipman fish, a model system for identifying the neural and endocrine basis of vocal-acoustic communication and alternative male reproductive tactics. Here, we quantified seasonal changes in brain aromatase mRNA expression in the inter- and intrasexually dimorphic sonic motor nucleus (SMN) and in the preoptic area (POA) in males and females in relation to seasonal changes in circulating steroid hormone levels and reproductive behaviors. Aromatase mRNA expression was compared within each sex throughout non-reproductive, pre-nesting, and nesting periods as well as between sexes within each season. Intrasexual (male) differences were also compared within the nesting period. Females had higher mRNA levels in the pre-nesting period when their steroid levels peaked, while acoustically courting (type I) males had highest expression during the nesting period when their steroid levels peaked. Females had significantly higher levels of expression than type I males in all brain areas, but only during the pre-nesting period. During the nesting period, non-courting type II males had significantly higher levels of aromatase mRNA in the SMN but equivalent levels in the POA compared to type I males and females. These results demonstrate seasonal and sex differences in brain aromatase mRNA expression in a teleost fish and suggest a role for aromatase in the expression of vocal-acoustic and alternative male reproductive phenotypes. © 2005 Wiley Periodicals, Inc. J. Neurobiol, 2005 [source]

Role of oxytocin and vasopressin in the transitions of weaning in the rat

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2004
A. Kavushansky
Abstract Sucklings (18-day-old) and weanlings (35-day-old) were injected icv with oxytocin or its antagonist (both 0.5 ,g/1 ,l), or vasopressin (1.0 ng/1 ,l) or its antagonist (100 ng/1 ,l), prior to 4-min observation in a behavioral maze with a sibling in one box and their anesthetized dam in the other. Oxytocin abolished nipple attachment in sucklings, decreased time spent with the dam, and increased self-grooming. The oxytocin antagonist had little influence on behavior. Vasopressin increased self-grooming while its antagonist reduced passive contact with the dam, increased active contact with her, and increased exploration and activity. We conclude that these neuropeptides have diverse roles during weaning, maintaining sucklings' behavior or promoting weaning, and subserving the transition from attachment to the dam to independence from her. We propose that these neurochemicals, and others, mediate the neural, affiliative, and affective changes of weaning, and that the term "weaning" should be understood to encompass these behavioral transitions. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 231,238, 2004. [source]

Diabetic neuropathy and oxidative stress

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2006
Rodica Pop-Busui
Abstract This review will focus on the impact of hyperglycemia-induced oxidative stress in the development of diabetes-related neural dysfunction. Oxidative stress occurs when the balance between the production of reactive oxygen species (ROS) and the ability of cells or tissues to detoxify the free radicals produced during metabolic activity is tilted in the favor of the former. Although hyperglycemia plays a key role in inducing oxidative stress in the diabetic nerve, the contribution of other factors, such as endoneurial hypoxia, transition metal imbalances, and hyperlipidemia have been also suggested. The possible sources for the overproduction of ROS in diabetes are widespread and include enzymatic pathways, auto-oxidation of glucose, and mitochondrial superoxide production. Increase in oxidative stress has clearly been shown to contribute to the pathology of neural and vascular dysfunction in diabetes. Potential therapies for preventing increased oxidative stress in diabetic nerve dysfunction will be discussed. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Melanoma with cartilaginous differentiation: Diagnostic challenge on fine-needle aspiration with emphasis on differential diagnosis

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2009
Krisztina Z. Hanley M.D.
Abstract Fine-needle aspiration (FNA) is a minimally invasive, fast, and accurate diagnostic method for the evaluation of patients with locally recurrent or distant metastases of malignant melanoma. In the vast majority of cases, the diagnosis is straightforward with the characteristic cytologic features well documented in the literature. Divergent differentiation (chondroid, neural, myofibroblastic, and osteocartilagenous) in a melanoma is rare and can potentially create diagnostic challenges if the evaluator is unaware of the same. We report a case of a 46-year-old female with a history of primary anal melanoma who presented with a groin mass. The FNA of the groin mass showed a neoplasm rich in chondroid matrix and raised the possibility of a second primary mesenchymal neoplasm rather than metastasis from the patient's known primary anal melanoma. A review of the histologic features of the anal melanoma showed divergent chondroid differentiation in the anal melanoma with the metastatic deposit in the groin exhibiting extensive chondroid differentiation. The differential diagnostic considerations are discussed. Diagn. Cytopathol. 2009. © 2008 Wiley-Liss, Inc. [source]

A neural network approach for structural identification and diagnosis of a building from seismic response data

EARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 2 2003
C. S. Huang
Abstract This work presents a novel procedure for identifying the dynamic characteristics of a building and diagnosing whether the building has been damaged by earthquakes, using a back-propagation neural network approach. The dynamic characteristics are directly evaluated from the weighting matrices of the neural network trained by observed acceleration responses and input base excitations. Whether the building is damaged under a large earthquake is assessed by comparing the modal parameters and responses for this large earthquake with those for a small earthquake that has not caused this building any damage. The feasibility of the approach is demonstrated through processing the dynamic responses of a five-storey steel frame, subjected to different strengths of the Kobe earthquake, in shaking table tests. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Structural damage detection using the optimal weights of the approximating artificial neural networks

EARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 2 2002
Shih-Lin Hung
Abstract This work presents a novel neural network-based approach to detect structural damage. The proposed approach comprises two steps. The first step, system identification, involves using neural system identification networks (NSINs) to identify the undamaged and damaged states of a structural system. The partial derivatives of the outputs with respect to the inputs of the NSIN, which identifies the system in a certain undamaged or damaged state, have a negligible variation with different system errors. This loosely defined unique property enables these partial derivatives to quantitatively indicate system damage from the model parameters. The second step, structural damage detection, involves using the neural damage detection network (NDDN) to detect the location and extent of the structural damage. The input to the NDDN is taken as the aforementioned partial derivatives of NSIN, and the output of the NDDN identifies the damage level for each member in the structure. Moreover, SDOF and MDOF examples are presented to demonstrate the feasibility of using the proposed method for damage detection of linear structures. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain?

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007
Clare Guilding
Abstract The suprachiasmatic nucleus of the hypothalamus (SCN) is the master circadian pacemaker or clock in the mammalian brain. Canonical theory holds that the output from this single, dominant clock is responsible for driving most daily rhythms in physiology and behaviour. However, important recent findings challenge this uniclock model and reveal clock-like activities in many neural and non-neural tissues. Thus, in addition to the SCN, a number of areas of the mammalian brain including the olfactory bulb, amygdala, lateral habenula and a variety of nuclei in the hypothalamus, express circadian rhythms in core clock gene expression, hormone output and electrical activity. This review examines the evidence for extra-SCN circadian oscillators in the mammalian brain and highlights some of the essential properties and key differences between brain oscillators. The demonstration of neural pacemakers outside the SCN has wide-ranging implications for models of the circadian system at a whole-organism level. [source]

The essential haematopoietic transcription factor Scl is also critical for neuronal development

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006
Cara K. Bradley
Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system; loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon; however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances; there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including ,-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues. [source]

Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005
Guy Gingras
Abstract Identification of the neural basis of the visual deficits experienced by humans with amblyopia, particularly when associated with strabismus (strabismic amblyopia), has proved to be difficult in part because of the inability to observe directly the neural changes at various levels of the human visual pathway. Much of our knowledge has necessarily been obtained on the basis of sophisticated psychophysical studies as well as from electrophysiological explorations on the visual pathways in animal models of amblyopia. This study combines these two approaches to the problem by employing similar psychophysical probes of performance on animal models of two forms of amblyopia (deprivation and strabismic) to those employed earlier on human amblyopes (Hess & Field, 1994, Vis. Res., 34, 13397,13406). The tests explore two competing explanations for the visual deficits, namely an evenly distributed loss of neural connections (undersampling) with the amblyopic eye as opposed to disordered connections with this eye (neural disarray). Unexpectedly, the results in animal models of deprivation amblyopia were not in accord with expectations based upon an even distribution of lost connections with the amblyopic eye. However, the results were similar to those observed in a strabismic amblyopic animal and to strabismic amblyopic humans. We suggest that deprivation amblyopia may be accompanied by an uneven loss of connections that results in effective neural disarray. By contrast, amblyopia associated with strabismus might arise from neural disarray of a different origin such as an alteration of intrinsic cortical connections. [source]

Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphology

GENES, BRAIN AND BEHAVIOR, Issue 3 2009
D. Leo
Methylphenidate (MPH) administration to adolescent rodents produces persistent region-specific changes in brain reward circuits and alterations of reward-based behavior. We show that these modifications include a marked increment of serotonin (5-hydroxy-tryptamine) receptor type 7 (Htr7) expression and synaptic contacts, mainly in the nucleus accumbens, and a reduction of basal behavioral impulsivity. We show that neural and behavioral consequences are functionally related: administration of a selective Htr7 antagonist fully counteracts the MPH-reduced impulsive behavior and enhances impulsivity when administered alone in naive rats. Agonist-induced activation of endogenous Htr7 significantly increases neurite length in striatal neuron primary cultures, thus suggesting plastic remodeling of neuronal morphology. The mixed Htr (1a/7) agonist, 8-OH-DPAT, reduces impulsive behavior in adolescent rats and in naive adults, whose impulsivity is enhanced by the Htr7 antagonist. In summary, behavioral pharmacology experiments show that Htr7 mediates self-control behavior, and brain primary cultures experiments indicate that this receptor may be involved in the underlying neural plasticity, through changes in neuronal cytoarchitecture. [source]

The utility of behavioral models and modules in molecular analyses of social behavior

GENES, BRAIN AND BEHAVIOR, Issue 3 2008
Andrew B. Barron
It is extremely difficult to trace the causal pathway relating gene products or molecular pathways to the expression of behavior. This is especially true for social behavior, which being dependent on interactions and communication between individuals is even further removed from molecular-level events. In this review, we discuss how behavioral models can aid molecular analyses of social behavior. Various models of behavior exist, each of which suggest strategies to dissect complex behavior into simpler behavioral ,modules.' The resulting modules are easier to relate to neural processes and thus suggest hypotheses for neural and molecular function. Here we discuss how three different models of behavior have facilitated understanding the molecular bases of aspects of social behavior. We discuss the response threshold model and two different approaches to modeling motivation, the state space model and models of reinforcement and reward processing. The examples we have chosen illustrate how models can generate testable hypotheses for neural and molecular function and also how molecular analyses probe the validity of a model of behavior. We do not champion one model over another; rather, our examples illustrate how modeling and molecular analyses can be synergistic in exploring the molecular bases of social behavior. [source]

A role for Connexin43 during neurodevelopment

GLIA, Issue 7 2007
Amy E. Wiencken-Barger
Abstract Connexin43 (Cx43) is the predominant gap junction protein expressed in premitotic radial glial cells and mature astrocytes. It is thought to play a role in many aspects of brain development and physiology, including intercellular communication, the release of neuroactive substances, and neural and glial proliferation and migration. To investigate the role of Cx43 in brain physiology, we generated a conditional knockout (cKO) mouse expressing Cre recombinase driven by the human GFAP promoter and a floxed Cx43 gene. The removal of Cx43 from GFAP-expressing cells affects the behavior of the mice and the development of several brain structures; however, the severity of the phenotype varies depending on the mouse background. One mouse subline, hereafter termed Shuffler, exhibits cellular disorganization of the cortex, hippocampus, and cerebellum, accompanied by ataxia and motor deficits. The Shuffler cerebellum is most affected and displays altered distribution and lamination of glia and neurons suggestive of cell migration defects. In all Shuffler mice by postnatal day two (P2), the hippocampus, cortex, and cerebellum are smaller. Disorganization of the ventricular and subventricular zone of the cortex is also evident. Given that these are sites of early progenitor cell proliferation, we suspect production and migration of neural progenitors may be altered. In conclusion, neurodevelopment of Shuffler/Cx43 cKO mice is abnormal, and the observed cellular phenotype may explain behavioral disturbances seen in these animals as well as in humans carrying Cx43 mutations. © 2007 Wiley-Liss, Inc. [source]

Contrasting roles of neural firing rate and local field potentials in human memory

HIPPOCAMPUS, Issue 8 2007
Arne Ekstrom
Abstract Recording the activity of neurons is a mainstay of animal memory research, while human recordings are generally limited to the activity of large ensembles of cells. The relationship between ensemble activity and neural firing rate during declarative memory processes, however, remains unclear. We recorded neurons and local field potentials (LFPs) simultaneously from the same sites in the human hippocampus and entorhinal cortex (ERC) in patients with implanted intracranial electrodes during a virtual taxi-driver task that also included a memory retrieval component. Neurons increased their firing rate in response to specific passengers or landmarks both during navigation and retrieval. Although we did not find item specificity in the broadband LFP, both ,- and ,-band LFPs increased power to specific items on a small but significant percent of channels. These responses, however, did not correlate with item-specific neural responses. To contrast item-specific responses with process-specific responses during memory, we compared neural and LFP responses during encoding (navigation) and retrieval (associative and item-specific recognition). A subset of neurons also altered firing rates nonspecifically while subjects viewed items during encoding. Interestingly, LFPs in the hippocampus and ERC increased in power nonspecifically while subjects viewed items during retrieval, more often during associative than item-recognition. Furthermore, we found no correlation between neural firing rate and broadband, ,-band, and ,-band LFPs during process-specific responses. Our findings suggest that neuronal firing and ensemble activity can be dissociated during encoding, item-maintenance, and retrieval in the human hippocampal area, likely relating to functional properties unique to this region. © 2007 Wiley-Liss, Inc. [source]

Human attachment security is mediated by the amygdala: Evidence from combined fMRI and psychophysiological measures

HUMAN BRAIN MAPPING, Issue 8 2006
Erwin Lemche
Abstract The neural basis of human attachment security remains unexamined. Using event-related functional magnetic resonance imaging (fMRI) and simultaneous recordings of skin conductance levels, we measured neural and autonomic responses in healthy adult individuals during a semantic conceptual priming task measuring human attachment security "by proxy". Performance during a stress but not a neutral prime condition was associated with response in bilateral amygdalae. Furthermore, levels of activity within bilateral amygdalae were highly positively correlated with attachment insecurity and autonomic response during the stress prime condition. We thereby demonstrate a key role of the amygdala in mediating autonomic activity associated with human attachment insecurity. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source]

Tunnel stability analysis during construction using a neuro-fuzzy system

INTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 15 2005
José Luis Rangel
Abstract This paper presents an alternative strategy to evaluate the stability of tunnels during the design and construction stages based on a hybrid system, composed by neural, neuro-fuzzy and analytical solutions. A prototype of this system is designed using a database formed by 261 cases, 45 real and the rest synthetic. This system is capable of reproducing the displacements induced at the periphery of the tunnel before and after support installation. The stability of the excavation process is evaluated using a criterion that considers dimensionless parameters based on the shear strength of the media, the induced deformation level in the ground, the plastic radii and the advance of excavation without support. The efficiency and validity of the prototype is verified with two examples of actual tunnels, one included in the database used to train the system and the other not included. The results of both examples show a better approximation than other commonly used techniques. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Circuits, computers, and beyond Boolean logic,

INTERNATIONAL JOURNAL OF CIRCUIT THEORY AND APPLICATIONS, Issue 5-6 2007
Tamás Roska
Abstract Historically, the invention of the stored programmable computer architecture, introduced by John Von Neumann, was also influenced by electrical circuit implementation aspects, as well as tied to fundamental insight of logic reasoning. It can also be considered as a mind-inspired machine. Since then, the implementation of logic gates, control and memories has developed independently of the architecture. The Cellular Wave Computer architecture (IEEE Trans. Circuits Syst. II 1993; 40:163,173; Electron. Lett. 2007; 43:427,449; J. Circuits Syst. Comput. 2003; 5(2):539,562) as a spatial,temporal universal machine on flows has also been influenced by circuit aspects of very large-scale integration (VLSI) technology, as well as some motivating living neural circuits, via the cellular nonlinear (neural) network (CNN). It might be considered as a brain-inspired machine. In this paper, after summarizing the main properties of the Cellular Wave Computer, we highlight a few basic properties of this new kind of computer and computing. In particular, phenomena related to (i) the one-pass solution of a set of implicit equations due to real-time spatial array feedback, (ii) the true random signal array generation via the insertion of the continuous physical noise signals, (iii) the finite synchrony radius due to the functional delay of wires, as well as to (iv) biology relevance. We also show that the Cellular Wave Computer is performing spatial,temporal inference that goes beyond Boolean logic, a characteristic of living neural circuits. Copyright © 2007 John Wiley & Sons, Ltd. [source]

A levenberg,marquardt learning applied for recurrent neural identification and control of a wastewater treatment bioprocess

INTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 11 2009
Ieroham S. Baruch
The paper proposed a new recurrent neural network (RNN) model for systems identification and states estimation of nonlinear plants. The proposed RNN identifier is implemented in direct and indirect adaptive control schemes, incorporating a noise rejecting plant output filter and recurrent neural or linear-sliding mode controllers. For sake of comparison, the RNN model is learned both by the backpropagation and by the recursive Levenberg,Marquardt (L,M) learning algorithm. The estimated states and parameters of the RNN model are used for direct and indirect adaptive trajectory tracking control. The proposed direct and indirect schemes are applied for real-time control of wastewater treatment bioprocess, where a good, convergence, noise filtering, and low mean squared error of reference tracking is achieved for both learning algorithms, with priority of the L,M one. © 2009 Wiley Periodicals, Inc. [source]