bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Pressor Area at the Medullo-Cervical Junction That Is Not Dependent on the RVLM: Efferent Pathways and Chemical Mediators
Authors: Seyedabadi Maryam , Li Qun , Padley James R. , Pilowsky Paul M. , Goodchild Ann K.
Published: May 2006

Chemical stimulation of a region extending from the most caudal ventrolateral medulla into the upper cervical spinal cord evoked large sympathetically mediated pressor responses. These responses were not dependent on the integrity of the rostral ventrolateral medulla (RVLM) and may be mediated by glutamatergic neurons embedded in the white matter that project to the thoracic spinal cord. We term this new region the medullo-cervical pressor area (MCPA). This region is distinct from the caudal pressor area, because blockade of the RVLM with muscimol inhibited this pressor response but not that evoked from the MCPA. This is the first study to provide functional evidence for a cardiovascular role for neurons in the cervical spinal cord white matter that innervate sympathetic preganglionic neurons (Jansen and Loewy, 1997). Using retrograde tracing, in combination with immunohistochemistry andin situhybridization, we identified two groups of spinally projecting neurons in the region. Approximately 50% of neurons in one group were excitatory because they contained vesicular glutamate transporter 1 (VGluT1)/VGluT2 mRNA, whereas the other contained a mixed population of neurons, some of which contained either VGluT1/VGluT2 or GAD67 (glutamic acid decarboxylase 67) mRNA. Despite the fact that activation of the MCPA causes potent sympathoexcitation, it does not act to restore arterial pressure after chemical lesion of the RVLM so that a role for this novel descending sympathoexcitatory region remains to be elucidated.
Necdin Promotes GABAergic Neuron Differentiation in Cooperation with Dlx Homeodomain Proteins
Authors: Kuwajima Takaaki , Nishimura Isao , Yoshikawa Kazuaki
Published: May 2006

Necdin, a member of the MAGE (melanoma antigen) protein family, is expressed predominantly in terminally differentiated neurons. The necdin geneNDNis maternally imprinted and expressed only from the paternal allele, the deficiency of which is implicated in the pathogenesis of the neurodevelopmental disorder Prader-Willi syndrome. Necdin binds to its homologous MAGE protein MAGE-D1 (also known as NRAGE or Dlxin-1), which interacts with Msx (msh homeobox) and Dlx (distal-less homeobox) family homeodomain transcription factors. Members of the Dlx homeobox gene family are involved in the differentiation and specification of forebrain GABAergic neurons. Here we demonstrate that necdin associates with Dlx homeodomain proteins via MAGE-D1 to promote the differentiation of GABAergic neurons in mouse embryonic forebrain. Immunohistochemical analysis revealed that necdin was coexpressed with Dlx2, Dlx5, or MAGE-D1 in a subpopulation of embryonic forebrain cells. Necdin bound to Dlx2 and Dlx5 via MAGE-D1 and enhanced Dlx2-dependent activation of the Wnt1 (wingless-type MMTV integration site family) promoter. Necdin significantly increased the populations of cells expressing the GABAergic neuron markers calbindin D-28k and glutamic acid decarboxylase when overexpressed by electroporation in cultured forebrain slices. In this assay, Dlx5N, a truncated Dlx5 mutant that competes with Dlx2 to bind MAGE-D1, diminished the effect of necdin on GABAergic neuron differentiation. Furthermore, mutant mice lacking the paternal necdin allele showed a significant reduction in the differentiation of forebrain GABAergic neuronsin vivoandin vitro. These results suggest that paternally expressed necdin facilitates the differentiation and specification of GABAergic neurons in cooperation with Dlx homeodomain proteins.
Brain Activation during Input from Mechanoinsensitive versus Polymodal C-Nociceptors
Authors: Ruehle Belinda Susanne , Handwerker Hermann Otto , Lennerz Jochen Klaus Maria , Ringler Ralf , Forster Clemens
Published: May 2006

C-nociceptors mediating cutaneous pain in humans can be distinguished in mechano-heat-responsive units (CMH) and mechano-insensitive units (CMi). However, if sensitized in damaged tissue, CMiplay an important role in inflammatory pain. CMidiffer from CMH by higher electrical thresholds and by mediating the axon reflex. Using these properties, we established two stimulation paradigms: (1) transcutaneous stimulation (TCS) of low current density below the CMithreshold and (2) intracutaneous stimulation (ICS) of high current density that excites CMi. This was proven by the quantification of the axon-reflex flare. Applying these stimulation paradigms during functional magnetic resonance imaging, we investigated whether nociceptor stimulation that recruits CMileads to different cerebral activation than stimuli that do not recruit CMi. Brain activation by CMiwas inferred by subtraction. Both stimuli recruited multiple afferents other than CMi, and we expected a common network of regions involved in different aspects of pain perception and motor nocifensive reactions in both stimuli. ICS that additionally recruited CMishould activate regions with low acuity that are involved in pain memory and emotional attribution. Besides a common network of pain in both stimuli, TCS activated the supplementary motor area, motor thalamic nuclei, the ipsilateral insula, and the medial cingulate cortex. These regions contribute to a pain processing loop that coordinates the nocifensive motor reaction. CMinociceptor activation did not cause relevant activation in this loop and does not seem to play a role in withdrawal. The posterior cingulate cortex was selectively activated by ICS and is apparently important for the processing of inflammatory pain.
Context Fear Learning in the Absence of the Hippocampus
Authors: Wiltgen Brian J. , Sanders Matthew J. , Anagnostaras Stephan G. , Sage Jennifer R. , Fanselow Michael S.
Published: May 2006

Lesions of the rodent hippocampus invariably abolish context fear memories formed in the recent past but do not always prevent new learning. To better understand this discrepancy, we thoroughly examined the acquisition of context fear in rats with pretraining excitotoxic lesions of the dorsal hippocampus. In the first experiment, animals received a shock immediately after placement in the context or after variable delays. Immediate shock produced no context fear learning in lesioned rats or controls. In contrast, delayed shock produced robust context fear learning in both groups. The absence of fear with immediate shock occurs because animals need time to form a representation of the context before shock is presented. The fact that it occurs in both sham and lesioned rats suggests that they learn about the context in a similar manner. However, despite learning about the context in the delay condition, lesioned rats did not acquire as much fear as controls. The second experiment showed that this lesion-induced deficit could be overcome by increasing the number of conditioning trials. Lesioned animals learned normally after multiple shocks, regardless of freezing level or trial spacing. The last experiment showed that animals with complete hippocampus lesions could also learn about the context, although the same lesions produced devastating retrograde amnesia. These results demonstrate that alternative systems can acquire context fear but do so less efficiently than the hippocampus.
An Inhibitor of DNA Recombination Blocks Memory Consolidation, But Not Reconsolidation, in Context Fear Conditioning
Authors: Colón-Cesario Melissa , Wang Jianpeng , Ramos Xiomara , García Hermes G. , Dávila Jorge J. , Laguna Jessenia , Rosado Claribel , Peña de Ortiz Sandra
Published: May 2006

Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-β-d-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligase-dependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.
Small, Nonpeptide p75NTRLigands Induce Survival Signaling and Inhibit proNGF-Induced Death
Authors: Massa Stephen M. , Xie Youmei , Yang Tao , Harrington Anthony W. , Kim Mi Lyang , Yoon Sung Ok , Kraemer Rosemary , Moore Laura A. , Hempstead Barbara L. , Longo Frank M.
Published: May 2006

Studies showing that neurotrophin binding to p75NTRcan promote cell survival in the absence of Trk (tropomyosin-related kinase) receptors, together with recent structural data indicating that NGF may bind to p75NTRin a monovalent manner, raise the possibility that small molecule p75NTRligands that positively regulate survival might be found. A pharmacophore designed to capture selected structural and physical chemical features of a neurotrophin domain known to interact with p75NTRwas applied toin silicoscreening of small molecule libraries. Small, nonpeptide, monomeric compounds were identified that interact with p75NTR. In cells showing trophic responses to neurotrophins, the compounds promoted survival signaling through p75NTR-dependent mechanisms. In cells susceptible to proneurotrophin-induced death, compounds did not induce apoptosis but inhibited proneurotrophin-mediated death. These studies identify a unique range of p75NTRbehaviors that can result from isolated receptor liganding and establish several novel therapeutic leads.
Urocortin 2-Deficient Mice Exhibit Gender-Specific Alterations in Circadian Hypothalamus–Pituitary–Adrenal Axis and Depressive-Like Behavior
Authors: Chen Alon , Zorrilla Eric , Smith Sean , Rousso David , Levy Coree , Vaughan Joan , Donaldson Cindy , Roberts Amanda , Lee Kuo-Fen , Vale Wylie
Published: May 2006

Gender differences in hypothalamus–pituitary–adrenal (HPA) axis activation and the prevalence of mood disorders are well documented. Urocortin 2, a recently identified member of the corticotropin-releasing factor family, is expressed in discrete neuroendocrine and stress-related nuclei of the rodent CNS. To determine the physiological role of urocortin 2, mice null for urocortin 2 were generated and HPA axis activity, ingestive, and stress-related behaviors and alterations in expression levels of CRF-related ligands and receptors were examined. Here we report that female, but not male, mice lacking urocortin 2 exhibit a significant increase in the basal daily rhythms of ACTH and corticosterone and a significant decrease in fluid intake and depressive-like behavior. The differential phenotype of urocortin 2 deficiency in female and male mice may imply a role for urocortin 2 in these gender differences.
Phosphatidylinositol 3 Kinase Activation and AMPA Receptor Subunit Trafficking Underlie the Potentiation of Miniature EPSC Amplitudes Triggered by the Activation of L-Type Calcium Channels
Authors: Baxter Andrew W. , Wyllie David J. A.
Published: May 2006

We have characterized a mechanism by which the amplitudes of miniature EPSCs (mEPSCs) in CA1 pyramidal neurons in rat hippocampal organotypic slice cultures are potentiated by approximately twofold after a series of depolarizing voltage pulses from –80 to +20 mV. The increase in mEPSC amplitudes is triggered by the activation of L-type calcium channels and is independent of NMDA receptor (NMDAR) activation but also requires calcium release from intracellular stores. The potentiation induced by depolarizing pulses does not alter the kinetic parameters of mEPSCs. The induction phase of this potentiation involves phosphatidylinositol 3 kinase (PI3 kinase) activation because it is blocked completely in the presence of the PI3 kinase inhibitors wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Furthermore, we show that the maintenance phase of depolarizing pulse potentiation requires continued PI3 kinase activity because the application of either wortmannin or LY294002 results in a reversal to control levels of the amplitudes of mEPSCs. Finally, we demonstrate that the increase in mEPSC amplitudes is mediated by the increased expression of functional AMPA receptors (AMPARs) because the potentiation is blocked byN-ethylmaleimide, botulinum toxin A, and a variety of short-sequence peptides that disrupt the interaction of AMPAR subunits with proteins involved with the trafficking of these to the cell membrane. Our data are consistent with the notion that PI3 kinase and membrane fusion/trafficking events play a pivotal role in coordinating changes in synaptic strength, mediated by AMPA receptors, which are triggered by alterations in postsynaptic calcium concentrations whether these changes are initiated via NMDAR-dependent or NMDAR-independent routes.
Symmetry of Cortical Folding Abnormalities in Williams Syndrome Revealed by Surface-Based Analyses
Authors: Van Essen David C. , Dierker Donna , Snyder A. Z. , Raichle Marcus E. , Reiss Allan L. , Korenberg Julie
Published: May 2006

We analyzed folding abnormalities in the cerebral cortex of subjects with Williams syndrome (WS), a genetically based developmental disorder, using surface-based analyses applied to structural magnetic resonance imaging data. Surfaces generated from each individual hemisphere were registered to a common atlas target (the PALS-B12 atlas). Maps of sulcal depth (distance from the cerebral hull) were combined across individuals to generate maps of average sulcal depth for WS and control subjects, along with depth-difference maps andt-statistic maps that accounted for within-group variability. Significant structural abnormalities were identified in 33 locations, arranged as 16 bilaterally symmetric pairs plus a lateral temporal region in the right hemisphere. Discrete WS folding abnormalities extended across a broad swath from dorsoposterior to ventroanterior regions of each hemisphere, in cortical areas associated with multiple sensory modalities as well as regions implicated in cognitive and emotional behavior. Hemispheric asymmetry in the temporal cortex is reduced in WS compared with control subjects. These findings provide insights regarding possible developmental mechanisms that give rise to folding abnormalities and to the spectrum of behavioral characteristics associated with WS.
Combined Application of Behavior Genetics and Microarray Analysis to Identify Regional Expression Themes and Gene–Behavior Associations
Authors: Letwin Noah E. , Kafkafi Neri , Benjamini Yoav , Mayo Cheryl , Frank Bryan C. , Luu Troung , Lee Norman H. , Elmer Greg I.
Published: May 2006

In this report we link candidate genes to complex behavioral phenotypes by using a behavior genetics approach. Gene expression signatures were generated for the prefrontal cortex, ventral striatum, temporal lobe, periaqueductal gray, and cerebellum in eight inbred strains from priority group A of the Mouse Phenome Project. Bioinformatic analysis of regionally enriched genes that were conserved across all strains revealed both functional and structural specialization of particular brain regions. For example, genes encoding proteins with demonstrated anti-apoptotic function were over-represented in the cerebellum, whereas genes coding for proteins associated with learning and memory were enriched in the ventral striatum, as defined by the Expression Analysis Systematic Explorer (EASE) application. Association of regional gene expression with behavioral phenotypes was exploited to identify candidate behavioral genes. Phenotypes that were investigated included anxiety, drug-naive and ethanol-induced distance traveled across a grid floor, and seizure susceptibility. Several genes within the glutamatergic signaling pathway (i.e., NMDA/glutamate receptor subunit 2C, calmodulin, solute carrier family 1 member 2, and glutamine synthetase) were identified in a phenotype-dependent and region-specific manner. In addition to supporting evidence in the literature, many of the genes that were identified could be mappedin silicoto surrogate behavior-related quantitative trait loci. The approaches and data set described herein serve as a valuable resource to investigate the genetic underpinning of complex behaviors.
Neural Lineages of theDrosophilaBrain: A Three-Dimensional Digital Atlas of the Pattern of Lineage Location and Projection at the Late Larval Stage
Authors: Pereanu Wayne , Hartenstein Volker
Published: May 2006

The late larval brain consists of embryonically produced primary neurons forming a deep core cortex, surrounded at the surface by ∼100 secondary lineages. Each secondary lineage forms a tract (secondary lineage tract) with an invariant and characteristic trajectory. Within the neuropile, tracts of neighboring lineages bundle together to form secondary tract systems. In this paper, we visualized secondary lineages by the global marker BP106 (neurotactin), as well as green fluorescent protein-labeled clones and thereby establish a comprehensive digital atlas of secondary lineages. The information contained in this atlas is the location of the lineage within the cortex, the neuropile compartment contacted by the lineage tract, and the projection pattern of the lineage tract within the neuropile. We have digitally mapped the expression pattern of three genes,sine oculis,period, andengrailedinto the lineage atlas. The atlas will enable us and others to analyze the phenotype of mutant clones in the larval brain. Mutant clones can only be interpreted if the corresponding wild-type clone is well characterized, and our lineage atlas, which visualizes all wild-type lineages, will provide this information. Secondly, secondary lineage tracts form a scaffold of connections in the neuropile that foreshadows adult nerve connections. Thus, starting from the larval atlas and proceeding forward through pupal development, one will be able to reconstruct adult brain connectivity at a high level of resolution. Third, the atlas can serve as a repository for genes expressed in lineage-specific patterns.
Role of Dopamine in the Primate Caudate Nucleus in Reward Modulation of Saccades
Authors: Nakamura Kae , Hikosaka Okihide
Published: May 2006

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position–reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus.
Glucocorticoid Hormones Decrease Proliferation of Embryonic Neural Stem Cells through Ubiquitin-Mediated Degradation of Cyclin D1
Authors: Sundberg Maria , Savola Suvi , Hienola Anni , Korhonen Laura , Lindholm Dan
Published: May 2006

Corticosteroids can influence brain function, and glucocorticoid hormone receptors (GRs) are present in brain tissue. We observed that GR and also mineralocorticoid receptor (MR) are expressed by embryonic rat neural stem cells (NSCs). NSCs in developing ventricular epithelium were positive for GR. Stimulation of cultured NSCs with the specific receptor ligands dexamethasone and corticosterone reduced cell proliferation, shown by 5′-bromo-2-deoxy-uridine labeling. The effect of the hormones was dose dependent and inhibited by the GR blocker mifepristone but not by spironolactone, blocking MR. Dexamethasone inhibited the cell cycle by decreasing the levels of cyclin D1 in NSCs. The hormone-induced decline was inhibited by MG132 (benzyloxycarbonyl-leucyl-leucyl-leucinal), showing an involvement of the ubiquitin proteasome system, In keeping with this, dexamethasone increased the ubiquitination of cyclin D1. In embryonic brain, dexamethasone inhibited cell proliferation of NSCs. This demonstrates that embryonic NSCs are critically influenced by glucocorticoids, which can have long-term effects in the brain.
Activity of Renshaw Cells during Locomotor-Like Rhythmic Activity in the Isolated Spinal Cord of Neonatal Mice
Authors: Nishimaru Hiroshi , Restrepo Carlos E. , Kiehn Ole
Published: May 2006

In the present study, we examine the activity patterns of and synaptic inputs to Renshaw cells (RCs) during fictive locomotion in the newborn mouse using visually guided recordings from GABAergic cells expressing glutamic acid decarboxylase 67–green fluorescent protein (GFP). Among the GFP-positive neurons in the lumbar ventral horn, RCs were uniquely identified as receiving ventral root-evoked short-latency EPSPs that were markedly reduced in amplitude by nicotinic receptor blockers mecamylamine or tubocurarine. During locomotor-like rhythmic activity evoked by bath application of 5-HT and NMDA, 50% of the recorded RCs fired in-phase with the ipsilateral L2 flexor-related rhythm, whereas the rest fired in the extensor phase. Each population of RCs fired throughout the corresponding locomotor phase. All RCs received both excitatory and inhibitory synaptic inputs during the locomotor-like rhythmic activity. Blocking nicotinic receptors with mecamylamine markedly reduced the rhythmic excitatory drive, indicating that these rhythmic inputs originate mainly from motor neurons (MNs). Inhibitory synaptic inputs persisted in the presence of the nicotinic blocker. Part of this inhibitory drive and remaining excitatory drive could be from commissural interneurons because the present study also shows that RCs receive direct crossed inhibitory and excitatory synaptic inputs. However, rhythmic synaptic inputs in RCs were also observed in hemicord preparations in the presence of mecamylamine. These results show that, during locomotor activity, RC firing properties are modulated not only by MNs but also by the ipsilateral and contralateral locomotor networks.
Early Life Blockade of 5-Hydroxytryptamine 1A Receptors Normalizes Sleep and Depression-Like Behavior in Adult Knock-Out Mice Lacking the Serotonin Transporter
Authors: Alexandre Chloé , Popa Daniela , Fabre Véronique , Bouali Saoussen , Venault Patrice , Lesch Klaus-Peter , Hamon Michel , Adrien Joëlle
Published: May 2006

In serotonin transporter knock-out (5-HTT−/−) mice, extracellular serotonin (5-HT) levels are markedly elevated in the brain, and rapid eye movement sleep (REMS) is enhanced compared with wild-type mice. We hypothesized that such sleep impairment at adulthood results from excessive serotonergic tone during early life. Thus, we assessed whether neonatal treatment with drugs capable of limiting the impact of 5-HT on the brain could normalize sleep patterns in 5-HTT−/− mutants. We found that treatments initiated at postnatal day 5 and continued for 2 weeks with the 5-HT synthesis inhibitorpara-chlorophenylalanine, or for 4 weeks with the 5-HT1Areceptor (5-HT1AR) antagonistN-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635), induced total or partial recovery of REMS, respectively, in 5-HTT−/− mutants. Early life treatment with WAY 100635 also reversed the depression-like behavior otherwise observed in these mutants. Possible adaptive changes in 5-HT1AR after neonatal treatment with WAY 100635 were investigated by measuring 5-HT1Abinding sites and 5-HT1AmRNA in various REMS- and/or depression-related brain areas, as well as 5-HT1AR-mediated hypothermia and inhibition of neuronal firing in the dorsal raphe nucleus. None of these characteristics were modified in parallel with REMS recovery, suggesting that 5-HT1ARs involved in wild-type phenotype rescue in 5-HTT−/− mutants are located in other brain areas or in 5-HT1AR-unrelated circuits where they could be transiently expressed during development. The reversal of sleep alterations and depression-like behavior after early life blockade of 5-HT1AR in 5-HTT−/− mutants might open new perspectives regarding preventive care of sleep and mood disorders resulting from serotonin transporter impairments during development.
Dendritic Calcium Spikes Are Tunable Triggers of Cannabinoid Release and Short-Term Synaptic Plasticity in Cerebellar Purkinje Neurons
Authors: Rancz Ede A. , Häusser Michael
Published: May 2006

Understanding the relationship between dendritic excitability and synaptic plasticity is vital for determining how dendrites regulate the input–output function of the neuron. Dendritic calcium spikes have been associated with the induction of long-term changes in synaptic efficacy. Here we use direct recordings from cerebellar Purkinje cell dendrites to show that synaptically activated local dendritic calcium spikes are potent triggers of cannabinoid release, producing a profound and short-term reduction in synaptic efficacy at parallel fiber synapses. Enhancing dendritic excitability by modulating dendritic large-conductance calcium-activated potassium (BK) channels improves the spread of dendritic calcium spikes and enhances cannabinoid release at the expense of spatial specificity. Our findings reveal that dendritic calcium spikes provide a local and tunable coincidence detection mechanism that readjusts synaptic gain when synchronous activity reaches a threshold, and they reveal a tight link between the regulation of dendritic excitability and the induction of synaptic plasticity.
Linear Summation of Cat Motor Cortex Outputs
Authors: Ethier Christian , Brizzi Laurent , Darling Warren G. , Capaday Charles
Published: May 2006

Recruitment of movement-related muscle synergies involves the functional linking of motor cortical points. We asked how the outputs of two simultaneously stimulated motor cortical points would interact. To this end, experiments were done in ketamine-anesthetized cats. When prolonged (e.g., 500 ms) trains of intracortical microstimulation were applied in the primary motor cortex, stimulus currents as low as 10–20 μA evoked coordinated movements of the contralateral forelimb. Paw kinematics in three dimensions and the electromyographic (EMG) activity of eight muscles were simultaneously recorded. We show that the EMG outputs of two cortical points simultaneously stimulated are additive. The movements were represented as displacement vectors pointing from initial to final paw position. The displacement vectors resulting from simultaneous stimulation of two cortical points pointed in nearly the same direction as the algebraic resultant vector. Linear summation of outputs was also found when inhibition at one of the cortical points was reduced by GABAAreceptor antagonists. A simple principle emerges from these results. Notwithstanding the underlying complex neuronal circuitry, motor cortex outputs combine nearly linearly in terms of movement direction and muscle activation patterns. Importantly, simultaneous activation does not change the nature of the output at each point. An additional implication is that not all possible movements need be explicitly represented in the motor cortex; a large number of different movements may be synthesized from a smaller repertoire.
The Anion-Selective Pore of the Bestrophins, a Family of Chloride Channels Associated with Retinal Degeneration
Authors: Qu Zhiqiang , Chien Li-Ting , Cui Yuanyuan , Hartzell H. Criss
Published: May 2006

Mutations in human bestrophin-1 (VMD2) are genetically linked to a juvenile form of macular degeneration and autosomal dominant vitreoretinochoroidopathy. Recently, it has been proposed that bestrophins are Cl−channels and that the putative second transmembrane domain participates in forming the bestrophin pore. However, the structural determinants of Cl−ion permeation through the channel pore are not known. Here we systematically replaced every amino acid in mouse bestrophin-2 (mBest2) between positions 69 and 104 with cysteine. We then measured the effects on the relative permeability and conductance of the channel to Cl−and SCN−(thiocyanate) and determined the accessibility of the cysteine-substituted amino acids to extracellularly applied, membrane-impermeant sulfhydryl reagents. Unlike K+channels, the amino acids forming the mBest2 selectivity filter are not discretely localized but are distributed over ∼20 amino acids within the transmembrane domain. Cysteine-substituted amino acids in the selectivity filter are easily accessible to extracellularly applied sulfhydryl reagents and select for anionic sulfhydryl reagents over cationic ones. Understanding the structure of the anion conduction pathway of bestrophins provides insights into how mutations produce channel dysfunction and may provide important information for development of therapeutic strategies for treating macular degeneration.
Synaptogenesis of the Calyx of Held: Rapid Onset of Function and One-to-One Morphological Innervation
Authors: Hoffpauir Brian K. , Grimes Janelle L. , Mathers Peter H. , Spirou George A.
Published: May 2006

Synaptogenesis during early development is thought to follow a canonical program whereby synapses increase rapidly in number and individual axons multiply-innervate nearby targets. Typically, a subset of inputs then out-competes all others through experience-driven processes to establish stable, long-lasting contacts. We investigated the formation of the calyx of Held, probably the largest nerve terminal in the mammalian CNS. Many basic functional and morphological features of calyx growth have not been studied previously, including whether mono-innervation, a hallmark of this system in adult animals, is established early in development. Evoked postsynaptic currents, recorded from neonatal mice between postnatal day 1 (P1) and P4, increased dramatically from −0.14 ± 0.04 nA at P1 to −6.71 ± 0.65 nA at P4 with sharp jumps between P2 and P4. These are the first functional assays of these nascent synapses for ages less than P3. AMPA and NMDA receptor-mediated currents were prominent across this age range. Electron microscopy (EM) revealed a concomitant increase, beginning at P2, in the prevalence of postsynaptic densities (16-fold) and adhering contacts (73-fold) by P4. Therefore, both functional and structural data showed that young calyces could form within 2 d, well before the onset of hearing around P8. Convergence of developing calyces onto postsynaptic targets, indicative of competitive processes that precede mono-innervation, was rare (4 of 29) at P4 as assessed using minimal stimulation electrophysiology protocols. Serial EM sectioning through 19 P4 cells further established the paucity (2 of 19) of convergence. These data indicate that calyces of Held follow a noncanonical program to establish targeted innervation that occurs over a rapid time course and precedes auditory experience.
Ultraviolet B Light Stimulates lnterleukin‐20 Expression by Human Epithelial Keratinocytes
Authors: Hunt David W. C. , Boivin Wendy A. , Fairley Lindsay A. , Jovanovic Miroslava M. , King Diane E. , Salmon Ruth A. , Utting Oliver B.
Published: May 2006

The proinflammatory cytokine interleukin‐20 (IL‐20) may exert the majority of its activity in the skin. We examined the effect of various treatments including several forms of phototherapy on IL‐20 expression using cultured normal human epithelial keratinocytes (NHEK). Broadband UVB light, recombinant (r) IL‐1 and rIL‐8 increased, while hydrocortisone reduced, NHEK supernatant IL‐20 levels. Elevation of NHEK IL‐20 mRNA and maximal supernatant IL‐20 levels occurred with a UVB light dose (40 mJ cm−2) that reduced cell viability by approximately 50%. While this UVB light dose also elevated supernatant IL‐1α and IL‐8 levels, antibody neutralization studies indicated that neither of these cytokines was directly responsible for this increase in IL‐20 expression. However, the elevation in IL‐20 levels was fully inhibited by the p38 mitogen‐activated protein kinase (MAPK) inhibitor SB‐203580, suggesting involvement of this stress signaling pathway in this UVB light response. Photodynamic therapy (PDT) with the photosensitizer lemuteporfin, UVA light, cisplatin, lipopolysaccharide (LPS), tumor necrosis factor‐α (TNF‐α) or recombinant interferon‐γ (rIFN‐γ) either had little effect or decreased NHEK supernatant IL‐20 levels. Reduced IL‐20 levels paralleled the cytotoxic actions of PDT, UVA light or cisplatin and the antiproliferative effect of rIFN‐γ. Neither rIL‐20 supplementation nor anti‐IL‐20 antibody treatments affected cell viability indicating that soluble IL‐20 did not affect the short‐term survival of UVB light‐irradiated NHEK. Stimulation of IL‐20 expression in keratinocytes by UVB light suggests that this cytokine might participate in skin responses to this ever‐present environmental factor and potentially has a role in UV light‐associated dermatoses.
Two‐Photon Singlet Oxygen Microscopy: The Challenges of Working with Single Cells
Authors: Skovsen Esben , Snyder John W. , Ogilby Peter R.
Published: May 2006

A microscope is described in which singlet molecular oxygen, O2(a 1Δg), is produced in a femtoliter focal volume via a nonlinear two‐photon photosensitized process, and the 1270 nm phosphorescence from this population of O2(a 1Δg) is detected in a photon counting experiment. Although two‐photon excitation of a sensitizer is less efficient than excitation by a one‐photon process, nonlinear excitation has several distinct advantages with respect to the spatial resolution accessible. Pertinent aspects of this two‐photon O2(a 1Δg) microscope were characterized using bulk solutions of photo‐sensitizers. These data were compared to those obtained from a single biological cell upon linear one‐photon excitation of a sensitizer incorporated in the cell. On the basis of the results obtained, we outline the challenges of using nonlinear optical techniques to create O2(a 1Δg) at the single cell level and to then optically detect the O2(a 1Δg) thus produced in a time‐resolved experiment.
New Strategies of Photoprotection
Authors: Verschooten Lien , Claerhout Sofie , Van Laethem An , Agostinis Patricia , Garmyn Marjan
Published: May 2006

Adequate photoprotection is essential to control UV‐related disorders, including sunburn, photoaging and photocarcinogenisis. Sun avoidance, protection of skin with clothing, and sunscreens are presently the best way of photoprotection, assuming that they are used properly. However, new strategies, which are based on or make use of the endogenous protective response to UV light, may further improve currently used photoprotective means. The addition of repair enzymes and/or antioxidants has a positive effect on skin's recovery from UV‐induced DNA‐damage. Several botanical agents, mainly vitamins and polyphenols, have shown to influence signal transduction pathways leading to photo‐protective effects. Also stimulation of endogenous UV‐response pathways via irradiation with a low UV dose or via simulation of UV‐induced DNA‐damage results in photo‐protective effects. Future research in this field and combination of different photoprotective strategies will hopefully lead to improved photoprotection.
SSR Markers Exhibit Trisomic Segregation Distortion in Soybean
Authors: Zou J. J. , Singh R. J. , Lee J. , Xu S. J. , Hymowitz T.
Published: May 2006

A primary trisomic (2n = 2x + 1) is an excellent cytogenetic tool to locate genes and associate linkage groups to their respective chromosomes in diploid plant species. In soybean [Glycine max (L.) Merr.], 11 molecular linkage groups (MLGs) were previously assigned to their respective chromosomes using simple sequence repeat (SSR) markers and primary trisomics. The chromosome location of the SSR markers was determined by altered segregation ratios from a disomic (1:2:1) to a trisomic genotypic ratio (6:11:1) in the F2 offspring derived from the crosses of soybean primary trisomics and G. soja Siebold & Zucc. In this study, we established the association between soybean Triplo 4 and MLG C1 based on trisomic segregation ratio (6:11:1) and cytological analysis. In addition, we identified four SSR markers that exhibited trisomic segregation distortion on three soybean chromosomes. Those SSR markers, including Satt565 and SOYGPATR on chromosome 4 (MLG C1), Satt193 on chromosome 13 (MLG F), and Satt226 on chromosome 17 (MLG D2) segregated in a 1:11:6 ratio, which is the reverse of the standard trisomic genotypic ratio. This is the first report of trisomic segregation distortion in soybean. Since G. max and G. soja usually differ either by a reciprocal translocation or by a paracentric inversion, we hypothesize that the genomic divergence between the two species and the numerically unbalanced genome in the trisomics might contribute to the distorted trisomic ratios. Genome instability may have been triggered in F1 primary trisomics causing unexpected trisomic inheritance in F2 Our results indicate that both normal and distorted trisomic segregation ratios should be considered when analyzing the association between chromosomes and linkage groups using primary trisomic analysis.
SIMULATED JURY DECISIONS: THE INFLUENCE OF JURY-DEFENDANT ATTITUDE SIMILARITY-DISSIMILARITY
Authors: Griffitt William , Jackson Thomas
Published: May 2006

Subjects were exposed to a standard videotape account of a crime of negligent automobile homicide. With the criminal evidence held constant, the similarity of the defendant's attitudes to those of simulated jury members was varied. Subjects exposed to a defendant with attitudes
dissimilar to their own rated the defendant as more guilty, sentenced him to a greater number of years of imprisonment, recommended lengthier terms of imprisonment prior to parole eligibility, and evaluated him less positively on measures of attraction and other evaluative dimensions, than
did subjects exposed to a defendant with attitudes similar to their own. The results are discussed with respect to evaluative response processes and judicial impartiality.
COGNITIVE STYLE PERFORMANCE AND FORM DISCRIMINATION
Authors: Vaught Glen M. , Roodin Paul A.
Published: May 2006

Forty-two male and 42 female college students were subdivided into field independent, medium, and field dependent identity groups and matched for sex. Each subject was given 24 active and 24 passive touch form discrimination trials. The results showed that active touch form discrimination
yielded fewer errors than passive touch and that females were better form discriminators than males. The interaction between field dependence, form discrimination and sex showed that in contrast to field independent subjects, field dependent males made more form discrimination errors while
females improved. This interaction is discussed in relation to the field dependence literature.
A RELATIONSHIP BETWEEN FIELD-DEPENDENCY-INDEPENDENCY AND SET: A WESTERN AND SOVIET VIEW
Authors: Hritzuk John , Taylor Lorne
Published: May 2006

Students were classed as field dependent or field independent using Witkin's Rod and Frame and the Embedded Figures Test. In addition, each of the 269 grade 8 subjects performed Uznadze's set tasks. The number of trials required for excitation and extinction in the haptic
and visual modality were noted. The field-dependent-independent groups, based on each test, were compared with their ability to excite and extinguish a set. A chi-square was used to test statistical significance. It was found that the field dependent and field independent groups differed in
their ability to extinguish a set but not to excite a set. The differences were interpreted as supporting Witkin's hypothesis involving Einstellung.
EFFECTS OF THE MULTI-DIMENSIONAL COMPOSITION OF EXTRAVERSION ON “FAKING BAD” ON THE EYSENCK PERSONALITY INVENTORY
Authors: Skinner Nicholas F.
Published: May 2006

Compared with scores obtained under standard directions, instructions to fake an “awful personality” on the Eysenck Personality Inventory produced significant increases in neuroticism and extraversion. An explanation for the unexpected increment in extraversion in terms
of the multi-factor composition of the E scale is discussed.
THE COMPLEXITY OF THE TARGET AS A FACTOR IN INTERPERSONAL JUDGEMENT
Authors: Adams-Webber J. R.
Published: May 2006

This study is concerned with the relation between accuracy in interpersonal judgment and the cognitive simplicity-complexity of the target. It was found that judges were significantly less accurate in inferring the self- characterizations of individuals who were assessed as high in
cognitive complexity on the basis of repertory grid analysis than those of persons who were assessed as either moderate or low in cognitive complexity.
SKIN CONDUCTANCE RESPONSES AND PERSONALITY DIMENSIONS -II
Authors: Adcock Ngaire V.
Published: May 2006

An attempt was made to confirm an earlier study in which SCR to electric shock had produced paradoxical results in relation to timidity, and to explore the possibility of making the procedure the basis for an objective test. A shortened procedure resulted in a similar response pattern,
but at too low a correlation level to be statistically significant or practically useful for testing purposes.
A FACTORIAL FACET ANALYSIS OF GOUGH'S SOCIALIZATION SCALE
Authors: Butt Dorcas Susan
Published: May 2006

Five subscales were isolated by factor analysis from Gough and Peterson's (1952) socialization scale. Four of these scales showed improved statistical adequacy and increased theoretical yield when compared with several total scale versions. The four subscales were: Family Stability,
Behavioral Control, Relaxed Security and Self-confidence.
A STUDY OF PERSONALITY: A WESTERN AND SOVIET POINT OF VIEW
Authors: Hritzuk John
Published: May 2006

A theoretical and experimental comparison is made of Eysenck's and Norakidze's work. The Soviet interpretation of set is a state of the subject in which prior events or activity conditions an individual to perceive stimuli or to react to stimuli in a specific manner. For Western
psychologists, set has varied meanings. Experimentally, hysterics and dysthymics significantly differ in set trials on Uznadze set tasks; however, the neurotics and non-neurotics, extraverts and introverts do not differ on set tasks.
MANIFESTATIONS OF MORAL DEVELOPMENT IN CONCRETE SITUATIONS
Authors: Butter Eliot J. , Sidenberg Bernard
Published: May 2006

One hundred college-age subjects were asked to present a recently, personally-experienced, moral conflict which was coded according to the stages of development elaborated by Kohlberg. The results indicated that the area of conflict is a factor affecting the level of maturity expressed
in the resolution of the conflict. Subjects experiencing political and ideological conflicts resolved these conflicts on a more mature level of development than subjects experiencing honesty or social conflicts. Subjects experiencing sexual conflicts also resolved them on a more mature level
than subjects experiencing honesty conflicts. No differences were found as a function of sex. Social conflicts were reported most often and legal conflicts least frequently. The results were discussed in terms of the differential responses to hypothetical and concrete moral conflicts.
INDIVIDUAL DIFFERENCES AMONG STUDENTS WHO MEET RESEARCH SUBJECT REQUIREMENTS EARLY VERSUS LATE IN THE TERM AS A SOURCE OF SAMPLING BIAS
Authors: Becker Gilbert
Published: May 2006

The predominant method of recruiting subjects for behavioral research in university settings permits students to choose which experiments of many to participate in. When this method is used, the possibility of sampling bias arises because some students make their choices early and others
late in the term. This study identified several Q-types (“ideographic” patterns derived from Q-factor analysis) that varied substantially with regard to choice time and thus offered suggestive evidence for a bias thesis. It was recommended that prevalent subject recruitment policy
be changed so that experimenters can arrange appointments on a random basis.
AROUSAL ROLE PLAYING AND PERSUASION
Authors: Kayne Harvey , Hendrick Clyde
Published: May 2006

Past research has indicated the existence of both positive and negative relationships between emotional arousal and persuasion. The present study is one of a series in a program designed to examine the relationships between extraneous arousal and persuasibility. Male and female subjects
role played either a relaxed or an aroused mood state, and then listened to a persuasive communication. Subjects' mood ratings were recorded both prior to and immediately following the communication. Attitudes and recall were assessed after the communication. Results indicated that the
role playing manipulation was successful in creating different moods. No arousal differences were found for the attitude measure, but significant sex differences were found. A weak negative relationship between arousal and attitude was found for female subjects. Factor analyses of the data
yielded potentially useful information regarding mood states and attitudes. The finding of a negative relationship between arousal and persuasion for females and virtually no relationship for males is comparable with other recent research. The present data provided tentative support for Leventhal'
(1970) parallel response model.
AN HIERARCHICAL OBLIQUE FACTOR ANALYSIS OF EYSENCK'S RATING STUDY OF 700 NEUROTICS
Authors: Howarth Edgar
Published: May 2006

Thirty-nine ratings were carried out on 700 neurotics and the data were factored but not rotated. These unrotated factors were interpreted by Eysenck (1944) as neuroticism, extraversion and hypochondriasis. These important data have been re-factored using hierarchical oblique factor
analysis, and the various solutions, beginning with the unrotated solution for comparison with the unrotated solution of Eysenck, are presented in detail. The interpretations from the rotated primary factors of this reanalysis do not agree with Eysenck?'s interpretations, which
have since been featured in his system. The second order solution proves to be a comparable obfuscation to the unrotated solution, in contrast to the clarity of the rotated primary factor solution.
CONDITIONING OF DEPRESSIVE RESPONSES
Authors: Welgan Peter R. , Fazio Anthony F.
Published: May 2006

An attempt was made to condition depressive responses through exposure to statements of depressing events. Behavioral measures of depression involved voice intensity, response latency and duration, as well as check list ratings and verbal reports. Experimental and demand characteristics
groups differed significantly in reports of depression compared with the neutral group. Results were discussed in terms of demand characteristics of the experiment, characteristics of the conditioning stimuli, and sensitivity of the response measures.