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Circuitry
Kinds of Circuitry Selected AbstractsCircuitry of nuclear factor ,B signalingIMMUNOLOGICAL REVIEWS, Issue 1 2006Alexander Hoffmann Summary:, Over the past few years, the transcription factor nuclear factor (NF)-,B and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-,B is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-,B's functioning in the immune system. NF-,B has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-,B is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-,B in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-,B functionalities involves system-wide measurements, biophysical studies, and computational modeling. [source] Neurophysiology of hunger and satietyDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008Pauline 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] Typical versus Atypical Absence Seizures: Network Mechanisms of the Spread of ParoxysmsEPILEPSIA, Issue 8 2007Jose L. Perez Velazquez Summary: Purpose: Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike-and-wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures. Methods: We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired-pulse paradigm. Results: In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike-and-wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired-pulse depression was then found in hippocampus of rats that displayed atypical absence seizures. Conclusions: These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures. [source] Postnatal handling alters the activation of stress-related neuronal circuitriesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000István M. Ábrahám Abstract Postnatal handling, as a crucial early life experience, plays an essential role in the development of hypothalamo-pituitary,adrenal axis responses to stress. The impact of postnatal handling on the reactivity of stress-related neuronal circuitries was investigated in animals that were handled for the first 21 days of life and as adults they were exposed to physical (ether) or emotional (restraint) challenge. To assess neuronal activation we relied on the induction of immediate-early gene product c-Fos and analysed its spatial and temporal distribution at various time intervals after stress. Ether and restraint commonly activated parvocellular neurons in the hypothalamic paraventricular nucleus, and resulted in activation of brain areas providing stress-related information to the hypothalamic effector neurons and/or in regions governing autonomic and behavioural responses to stress. Beyond these areas, the strength and timing of c-Fos induction showed stressor specificity in olfactory and septal region, basal ganglia, hypothalamus, hippocampal formation, amygdala and brainstem. Handled rats displayed a lower number of c-Fos-positive cell nuclei and weaker staining intensity than non-handled controls in the hypothalamic paraventricular nucleus, bed nucleus of stria terminalis, central nucleus of amygdala, hippocampus, piriform cortex and posterior division of the cingulum. Significant differences were revealed in timing of c-Fos induction as a function of stressor and early life experience. Together, these data provide functional anatomical evidence that environmental enrichment in the early postnatal period attenuates the reactivity of stress-related neuronal circuitries in the adult rat brain. [source] Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controlsTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 3 2009Rozmin Halari Background:, There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Methods:, Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14,17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results:, In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions:, This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD. [source] Pilot study of response inhibition and error processing in the posterior medial prefrontal cortex in healthy youthTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2008Kate Dimond Fitzgerald Background:, Recent neuroimaging work suggests that inhibitory and error processing in healthy adults share overlapping, but functionally distinct neural circuitries within the posterior medial frontal cortex (pMFC); however, it remains unknown whether the pMFC is differentially engaged by response inhibition compared to error commission in the developing brain. Developmental neuroimaging studies of response inhibition have found pMFC activation, but the possible contribution of error-related activation during inhibitory processing has not been well studied in youth. Method:, To examine the processing of correct response inhibition compared to errors in the developing brain, we performed functional magnetic resonance imaging scans in 11 healthy subjects, ages 8,14 years, during an antisaccade task while performance was monitored. Results:, Successful antisaccades activated the pre-supplementary motor area. In contrast, errors on the antisaccade task activated the dorsal anterior cingulate cortex. Conclusion:, The findings suggest the functional sub-specialization of inhibitory and error processing within the pMFC in this pilot sample of children and adolescents. Future neuroimaging studies of developing inhibitory control should examine both between correct and error trials. [source] Pharmacologic transgene control systems for gene therapyTHE JOURNAL OF GENE MEDICINE, Issue 5 2006Wilfried Weber Abstract Pharmacologic transgene-expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine-tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high-precision trigger-inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals. Availability of a portfolio of compatible transcription control systems has enabled assembly of higher-order control circuitries providing simultaneous or independent control of several transgenes and the design of (semi-)synthetic gene networks, which emulate digital expression switches, regulatory transcription cascades, epigenetic expression imprinting, and cellular transcription memories. This review provides an overview of cutting-edge developments in transgene control systems, of the design of synthetic gene networks, and of the delivery of such systems for the prototype treatment of prominent human disease phenotypes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancerTHE JOURNAL OF PATHOLOGY, Issue 5 2006C Gulmann Abstract The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular ,circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Location analysis of DNA-bound proteins at the whole-genome level: untangling transcriptional regulatory networksBIOESSAYS, Issue 6 2001Béatrice Nal In this post-sequencing era, geneticists can focus on functional genomics on a much larger scale than ever before. One goal is the discovery and elucidation of the intricate genetic networks that co-ordinate transcriptional activation in different regulatory circuitries. High-throughput gene expression measurement using DNA arrays has thus become routine strategy. This approach, however, does not directly identify gene loci that belong to the same regulatory group; e.g., those that are bound by a common (set of) transcription factor(s). Working in yeast, two groups have recently published an elegant method that could circumvent this problem, by combining chromatin immunoprecipitation and DNA microarrays.(1,2) The method is likely to provide a powerful tool for the dissection of global regulatory networks in eukaryotic cells. BioEssays 23:473,476, 2001. © 2001 John Wiley & Sons, Inc. [source] Ethanol neurotoxicity and dentate gyrus developmentCONGENITAL ANOMALIES, Issue 3 2008Takanori Miki ABSTRACT Maternal alcohol ingestion during pregnancy adversely affects the developing fetus, often leading to fetal alcohol syndrome (FAS). One of the most severe consequences of FAS is brain damage that is manifested as cognitive, learning, and behavioral deficits. The hippocampus plays a crucial role in such abilities; it is also known as one of the brain regions most vulnerable to ethanol-induced neurotoxicity. Our recent studies using morphometric techniques have further shown that ethanol neurotoxicity appears to affect the development of the dentate gyrus in a region-specific manner; it was found that early postnatal ethanol exposure causes a transitory deficit in the hilus volume of the dentate gyrus. It is strongly speculated that such structural modifications, even transitory ones, appear to result in developmental abnormalities in the brain circuitry and lead to the learning disabilities observed in FAS children. Based on reports on possible factors deciding ethanol neurotoxicity to the brain, we review developmental neurotoxicity to the dentate gyrus of the hippocampal formation. [source] Neuronismo y reticulismo: neuronal,glial circuits unify the reticular and neuronal theories of brain organizationACTA PHYSIOLOGICA, Issue 1 2009A. Verkhratsky Abstract The neuronal doctrine, which shaped the development of neuroscience, was born from a long-lasting struggle between reticularists, who assumed internal continuity of neural networks and neuronists, who defined the brain as a network of physically separated cellular entities, defined as neurones. Modern views regard the brain as a complex of constantly interacting cellular circuits, represented by neuronal networks embedded into internally connected astroglial syncytium. The neuronal,glial circuits endowed with distinct signalling cascades form a ,diffuse nervous net' suggested by Golgi, where millions of synapses belonging to very different neurones are integrated first into neuronal,glial,vascular units and then into more complex structures connected through glial syncytium. These many levels of integration, both morphological and functional, presented by neuronal,glial circuitry ensure the spatial and temporal multiplication of brain cognitive power. [source] Gender-specific disruptions in emotion processing in younger adults with depression,DEPRESSION AND ANXIETY, Issue 2 2009Sara L. Wright Ph.D. Abstract Background: One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. Methods: This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). Results: For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). Conclusions: These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc. [source] Circuits and systems in stress.DEPRESSION AND ANXIETY, Issue 1 2002Abstract This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD. Depression and Anxiety 16:14,38, 2002. © 2002 Wiley-Liss, Inc. [source] Environmental complexity and central nervous system development and functionDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004Mark H. Lewis Abstract Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical,basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus. MRDD Research Reviews 2004;10:91,95. © 2004 Wiley-Liss, Inc. [source] The effects of seizures on the connectivity and circuitry of the developing brainDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004John W. Swann Abstract Recurring seizures in infants and children are often associated with cognitive deficits, but the reason for the learning difficulties is unclear. Recent studies in several animal models suggest that seizures themselves may contribute in important ways to these deficits. Other studies in animals have shown that recurring seizures result in dendritic spine loss. This change, coupled with a down-regulation in NMDA receptor subunit expression, suggests that repetitive seizures may interrupt the normal development of glutamatergic synaptic transmission. We hypothesize that homeostatic, neuroprotective processes are induced by recurring early-life seizures. These processes, by diminishing glutamatergic synaptic transmission, are aimed at preventing the continuation of seizures. However, by preventing the normal development of glutamatergic synapses, and particularly NMDA receptor-mediated synaptic transmission, such homeostatic processes also reduce synaptic plasticity and diminish the ability of neuronal circuits to learn and store memories. MRDD Research Reviews 2004;10:96,100. © 2004 Wiley-Liss, Inc. [source] Expression of the ETS transcription factor ER81 in the developing chick and mouse hindbrainDEVELOPMENTAL DYNAMICS, Issue 3 2002Yan Zhu Abstract ER81 is an ETS domain-containing transcription factor, which is expressed in various developing tissues and organs of the embryo and in pools of developing spinal motor neurons and proprioceptive sensory neurons. Analysis of mice lacking ER81 function showed that this gene played an important role in the establishment of sensory-motor circuitry in the spinal cord. Here, we investigate the expression pattern of er81 in the hindbrain of both chick and mouse embryos. We find that er81 is expressed in a subpopulation of inferior olive neurons, which send their projections to the caudal cerebellum. © 2002 Wiley-Liss, Inc. [source] Neuromotor development in nocturnal enuresisDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2006Alexander von Gontard MD PhD In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y-14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y-14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis. [source] Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1DEVELOPMENTAL NEUROBIOLOGY, Issue 8 2010Bonnie M. Marsick Abstract Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism. However, it is unclear how guidance cues modify the cytoskeleton to guide growth cone pathfinding. Here, we show acute treatment with two attractive guidance cues, nerve growth factor (NGF) and netrin-1, for embryonic dorsal root ganglion and temporal retinal neurons, respectively, results in increased growth cone membrane protrusion, actin polymerization, and filamentous actin (F-actin). ADF/cofilin (AC) family proteins facilitate F-actin dynamics, and we found the inactive phosphorylated form of AC is decreased in NGF- or netrin-1-treated growth cones. Directly increasing AC activity mimics addition of NGF or netrin-1 to increase growth cone protrusion and F-actin levels. Extracellular gradients of NGF, netrin-1, and a cell-permeable AC elicit attractive growth cone turning and increased F-actin barbed ends, F-actin accumulation, and active AC in growth cone regions proximal to the gradient source. Reducing AC activity blunts turning responses to NGF and netrin. Our results suggest that gradients of NGF and netrin-1 locally activate AC to promote actin polymerization and subsequent growth cone turning toward the side containing higher AC activity. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 565,588, 2010 [source] Neuronal differentiation and long-term survival of newly generated cells in the olfactory midbrain of the adult spiny lobster, Panulirus argusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Manfred Schmidt Abstract The fate of continuously generated cells in the soma clusters of the olfactory midbrain of adult spiny lobsters, Panulirus argus, was investigated by in vivo pulse-chase experiments with the proliferation marker 5-bromo-2,-deoxyuridine (BrdU) combined with immunostainings for neuropeptides of mature neurons. A BrdU injection after a survival time (ST) of 14 h labeled about 100 nuclei in the lateral soma clusters (LC), comprised of projection neurons, and about 30 nuclei in the medial soma clusters (MC), comprised of local interneurons. The BrdU-positive nuclei were confined to small regions at the inside of these clusters, which also contain nuclei in different phases of mitosis and thus represent proliferative zones. After STs of 2 weeks or 3 months, the number of BrdU-positive nuclei was doubled, indicating a mitosis of all originally labeled cells. Dependent on ST, the BrdU-positive nuclei were translocated from the proliferative zones towards the outside of the clusters, where somata of mature neurons reside. Immunostainings with antibodies to the neuropeptides FMRFamide and substance P, both of which label a large portion of somata in the MC and a pair of giant neurons projecting into the LC, revealed that in both clusters the proliferative zones are surrounded by, but are themselves devoid of, labeling. In the MC, some BrdU-positive somata were double-labeled by the FMRFamide antibody after an ST of 3 months, and by the substance P antibody after STs of 6 and 11/14 months, but not after 3 months. In the LC, BrdU-positive somata after an ST of 3 months partially and after 6 and 11/14 months widely overlapped with the arborizations of the giant neurons, indicating the establishment of synaptic input. The experiments show that cells generated in proliferative zones in the LC and MC of adult spiny lobsters after a final mitosis differentiate into neurons within months, survive for at least 1 year, and are integrated into the circuitry of the olfactory midbrain. A new hypothesis about the mechanism of adult neurogenesis in the central olfactory pathway of decapod crustaceans is developed, linking it to neurogenesis during embryonic and larval development. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 181,203, 2001 [source] Motivational systems and the neural circuitry of maternal behavior in the ratDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2007Michael Numan Abstract Jay Rosenblatt's approach-avoidance model of maternal behavior proposes that maternal behavior occurs when the tendency to approach infant stimuli is greater than the tendency to avoid such stimuli. Our research program has uncovered neural circuits which conform to such a model. We present evidence that the medial preoptic area (MPOA: located in the rostral hypothalamus) may regulate maternal responsiveness by depressing antagonistic neural systems which promote withdrawal responses while also activating appetitive neural systems which increase the attractiveness of infant-related stimuli. These MPOA circuits are activated by the hormonal events of late pregnancy. Preoptic efferents may suppress a central aversion system which includes an amygdala to anterior hypothalamic circuit. Preoptic efferents are also shown to interact with components of the mesolimbic dopamine (DA) system to regulate proactive voluntary maternal responses. We make a distinction between specific (MPOA neurons) and nonspecific motivational systems (mesolimbic DA system) in the regulation of maternal responsiveness. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 49: 12,21, 2007. [source] Risk-taking and the adolescent brain: who is at risk?DEVELOPMENTAL SCIENCE, Issue 2 2007Adriana Galvan Relative to other ages, adolescence is described as a period of increased impulsive and risk-taking behavior that can lead to fatal outcomes (suicide, substance abuse, HIV, accidents, etc.). This study was designed to examine neural correlates of risk-taking behavior in adolescents, relative to children and adults, in order to predict who may be at greatest risk. Activity in reward-related neural circuitry in anticipation of a large monetary reward was measured with functional magnetic resonance imaging, and anonymous self-report ratings of risky behavior, anticipation of risk and impulsivity were acquired in individuals between the ages of 7 and 29 years. There was a positive association between accumbens activity and the likelihood of engaging in risky behavior across development. This activity also varied as a function of individuals' ratings of anticipated positive or negative consequences of such behavior. Impulsivity ratings were not associated with accumbens activity, but rather with age. These findings suggest that during adolescence, some individuals may be especially prone to engage in risky behaviors due to developmental changes in concert with variability in a given individual's predisposition to engage in risky behavior, rather than to simple changes in impulsivity. [source] Neuroanatomical basis for therapeutic applications of cannabinoid receptor 1 antagonistsDRUG DEVELOPMENT RESEARCH, Issue 8 2009Brian F. Thomas Abstract The CB1 receptor is a Class A G-protein coupled receptor that has a high density and widespread distribution within the central nervous system. Because of its neuroanatomical distribution, the endocannabinoid system can modulate a wide variety of psychological and physiological functions. For example, CB1 receptors are found in brain regions regulating motor activity, cognitive processes, pain, satiety, appetitive behaviors and reward. In correspondence with this distribution, modulation of the endocannabinoid system has been shown to produce changes in coordination, executive function, memory, mood, perception, wakefulness, nociception and appetite. Administration of cannabinoid agonists has also been therapeutically used to reduce nausea, and is also known to decrease body temperature and neuronal excitability, pointing to additional roles for endocannabinoids in these and other physiological/neurological processes. The ongoing elucidation and characterization of the neuroanatomical circuitry within which the CB1 cannabinoid receptor and endocannabinoids are localized to modulate these psychological and physiological processes continues to suggest therapeutic applications for cannabinoid antagonists and inverse agonists. Drug Dev Res 70:527,554, 2009. © 2009 Wiley-Liss, Inc. [source] Simple circuit to improve electric field homogeneity in contour-clamped homogeneous electric field chambersELECTROPHORESIS, Issue 7-8 2003José A. Herrera Abstract We redesigned contour-clamped homogeneous electric field (CHEF) circuitry to eliminate crossover distortion, to set identical potentials at electrodes of each equipotential pair and to drive pairs with transistors in emitter follower stages. An equipotential pair comprised the two electrodes set at the same potential to provide electric field homogeneity inside of the hexagonal array. The new circuitry consisted of two identical circuits, each having a resistor ladder, diodes and transistors. Both circuits were interconnected by diodes that controlled the current flow to electrodes when the array was energized in the ,A' or ,B' direction of the electric field. The total number of transistors was two-thirds of the total number of electrodes. Average voltage deviation from potentials expected at electrodes to achieve a homogeneous electric field was 0.06 V, whereas 0.44 V was obtained with another circuit that used transistors in push-pull stages. The new voltage clamp unit is cheap, generated homogeneous electric field, and gave reproducible and undistorted DNA band patterns. [source] Incentive-elicited striatal activation in adolescent children of alcoholicsADDICTION, Issue 8 2008James M. Bjork ABSTRACT Aims Deficient recruitment of motivational circuitry by non-drug rewards has been postulated as a pre-morbid risk factor for substance dependence (SD). We tested whether parental alcoholism, which confers risk of SD, is correlated with altered recruitment of ventral striatum (VS) by non-drug rewards in adolescence. Design During functional magnetic resonance imaging, adolescent children of alcoholics (COA; age 12,16 years) with no psychiatric disorders (including substance abuse) and similarly aged children with no risk factors responded to targets to win or avoid losing $0, $0.20, $1, $5 or a variable amount (ranging from $0.20 to $5). Results In general, brain activation by either reward anticipation or outcome notification did not differ between COA and age/gender-matched controls. Cue-elicited reward anticipation activated portions of VS in both COA and controls. In nucleus accumbens (NAcc), signal change increased with anticipated reward magnitude (with intermediate recruitment by variable incentives) but not with loss magnitudes. Reward deliveries activated the NAcc and mesofrontal cortex in both COA and controls. Losses activated anterior insula bilaterally in both groups, with more extensive right anterior insula activation by losses in controls. NAcc signal change during anticipation of maximum rewards (relative to non-reward) correlated positively with both Brief Sensation-Seeking Scale scores and with self-reported excitement in response to maximum reward cues (relative to cues for non-reward). Conclusions Among adolescents with no psychiatric disorders, incentive-elicited VS activation may relate more to individual differences in sensation-seeking personality than to presence of parental alcoholism alone. Future research could focus on adolescents with behavior disorders or additional risk factors. [source] Sodium channel SCN1A and epilepsy: Mutations and mechanismsEPILEPSIA, Issue 9 2010Andrew Escayg Summary Mutations in a number of genes encoding voltage-gated sodium channels cause a variety of epilepsy syndromes in humans, including genetic (generalized) epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS, severe myoclonic epilepsy of infancy). Most of these mutations are in the SCN1A gene, and all are dominantly inherited. Most of the mutations that cause DS result in loss of function, whereas all of the known mutations that cause GEFS+ are missense, presumably altering channel activity. Family members with the same GEFS+ mutation often display a wide range of seizure types and severities, and at least part of this variability likely results from variation in other genes. Many different biophysical effects of SCN1A -GEFS+ mutations have been observed in heterologous expression systems, consistent with both gain and loss of channel activity. However, results from mouse models suggest that the primary effect of both GEFS+ and DS mutations is to decrease the activity of GABAergic inhibitory neurons. Decreased activity of the inhibitory circuitry is thus likely to be a major factor contributing to seizure generation in patients with GEFS+ and DS, and may be a general consequence of SCN1A mutations. [source] Molecular and diffusion tensor imaging of epileptic networksEPILEPSIA, Issue 2008Aimee F. Luat Summary Several studies have shown that seizure-induced cellular and molecular changes associated with chronic epilepsy can lead to functional and structural alterations in the brain. Chronic epilepsy, when medically refractory, may be associated with an expansion of the epileptic circuitry to involve complex interactions between cortical and subcortical neuroanatomical substrates. Progress in neuroimaging has led not only to successful identification of epileptic foci for surgical resection, but also to an improved understanding of the functional and microstructural changes in long-standing epilepsy. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are all promising tools that can assist in elucidating the underlying pathophysiology in chronic epilepsy. Studies using PET scanning have demonstrated dynamic changes associated with the evolution from acute to chronic intractable epilepsy. Among these changes are data to support the existence of secondary epileptogenesis in humans. MRI with DTI is a powerful tool which has the ability to characterize microstructural abnormalities in epileptic foci, and to demonstrate the white matter fibers and tracts participating in the epileptic network. In this review, we illustrate how PET and DTI can be applied to depict the functional and microstructural alterations associated with chronic epilepsy. [source] Typical versus Atypical Absence Seizures: Network Mechanisms of the Spread of ParoxysmsEPILEPSIA, Issue 8 2007Jose L. Perez Velazquez Summary: Purpose: Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike-and-wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures. Methods: We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired-pulse paradigm. Results: In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike-and-wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired-pulse depression was then found in hippocampus of rats that displayed atypical absence seizures. Conclusions: These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures. [source] The Midline Thalamus: Alterations and a Potential Role in Limbic EpilepsyEPILEPSIA, Issue 8 2001Edward H. Bertram Summary: ,Purpose: In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. Results: The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration. Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits. [source] Role of Nitric Oxide in Pentylenetetrazol-Induced Seizures: Age-Dependent Effects in the Immature RatEPILEPSIA, Issue 4 2000Anne Pereira de Vasconcelos Summary: Purpose: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)-induced seizures in immature rats. Methods: Four cortical electrodes were implanted in 10-day-old (P10) and 21-day-old (P21) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of NG -nitro- l -arginine methyl ester (l -NAME; 10 mg/kg) and 7-nitroindazole (7NI; 40 mg/kg), two NO synthase (NOS) inhibitors, and l -arginine (l -arg; 300 mg/kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate. Results: At P10, the postseizure mortality rate increased from 18,29% for the rats receiving PTZ only to 100% and 89% for the rats receiving l -NAME and 7NI, respectively; whereas l -arg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82,89% mortality rate induced by PTZ alone, whereas l -arg decreased the mortality rate to 29%. In addition, all NO-related drugs increased the duration of ictal activity at P10, whereas at P21, L -arg and L -NAME affected the first seizure type, producing clonic seizures with L -arg and tonic seizures with L -NAME. Conclusions: The relative natural protection of very immature rats (P10) against PTZ-induced deaths could be linked to a high availability of L -arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO-related compounds may be related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of clonic seizures. [source] PRECLINICAL STUDY: Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chiralityADDICTION BIOLOGY, Issue 1 2010Nora Von Ameln ABSTRACT Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1,10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA. [source] | ||||||||||||||||||||||||||||||||||||||||