bluuebunny/crossref_metadata_2025 huggingface dataset:
Pertinencia territorial de las críticas al culturalismo
Authors: Aguilar Rivero Mariflor
Published: April 2018

La diversidad cultural ha ido ganando visibilidad, y con ello los movimientos sociales que de varias formas buscan hacerse escuchar. Al mismo tiempo se fue configurando el área de trabajo e investigación sobre los estudios culturales que buscaron abrir brecha para el reconocimiento de la identidad de las culturas. Sin embargo, en la línea contraria se desarrollan líneas de análisis que cuestionan los mismos estudios culturales. En este trabajo me voy a referir a algunos de los argumentos críticos al culturalismo para después tratar de pensar desde ellos la eficacia justificatoria de procesos de acumulación originaria que todavía azotan al país.
Filosofía y tiempo final
Authors: Subirats Eduardo
Published: April 2018

Revisar el efecto del 11 de septiembre como detonante de una nueva guerra global extendida públicamente a través de los mass media, y analizar las relaciones con el confinamiento individual, la dependencia de los medios electrónicos, el ecocidio sistemático y, principalmente, con la actual crisis del medio intelectual, son puntos centrales de este texto. La afirmación academicista del postestructuralismo, en la que el lenguaje se ostenta como única realidad legitimada, se enfrenta e impone a la creatividad y a la experiencia individual; de ello se desprenden consecuencias morales: nihilismo intelectual, constitución de la realidad como espectáculo, destrucción de culturas humanas con afanes colonialistas y destrucción de la naturaleza apoyada en el dominio científico y el poder tecnoindustrial. En el ensayo se reflexiona sobre la Teoría Crítica después del postmodernismo norteamericano, y sobre la inminencia del tiempo final contrastada con la estupidización masiva. Ante esto se plantea la recuperación de la esperanza como conocimiento activo y transformador; como el Prinzip Hoffnung de Ernst Bloch.
La mujer-filósofo o la más “antinatural” de las criaturas. En torno a Simone de Beauvoir y a su obra El segundo sexo
Authors: Guerra Palmero María José
Published: April 2018

El presente artículo analiza el carácter pionero de una de las obras clave del feminismo, El segundo sexo (1949), contribución fundamental a la filosofía feminista actual y primer marco teórico del feminismo de segunda ola. En este trabajo se analizarán los empleos de la categoría de alteridad para referirla a la existencia de las mujeres. El objetivo principal de la obra de Beauvoir es explicarnos y explicitarnos las condiciones de esa vida femenina expropiada y obligada a permanecer en la mera inmanencia. A partir de esta cuestión emergerá en el feminismo de la segunda ola la conceptualización constructivista de “género”. Exploramos, en segundo lugar, la recepción crítica de la obra de Simone de Beauvoir. La falta de reconocimiento, el descrédito y los prejuicios sexistas imposibilitaron hasta casi tres décadas después de su publicación su justa estimación crítica. Finalmente, se presta atención al des/encuentro entre dos generaciones de feministas francesas que representan la propia Simone de Beauvoir, Luce Irigaray y Michelle Le Doeuff.
Estudios de historia y de filosofía de las ciencias Georges Canguilhem Buenos Aires, Amorrortu Editores, 2009
Authors: Arriaga Pedro
Published: April 2018

Estudios de historia y de filosofía de las ciencias Georges Canguilhem Buenos Aires, Amorrortu Editores, 2009
Ironía, humor y grotesco. “Los relámpagos desmitificadores” y otros ensayos críticos. Ana Rosa Domenella México, El Colegio de México / Universidad Autónoma Metropolitana Iztapalapa, 2011
Authors: García Ortiz Luz de Lourdes
Published: April 2018

Ironía, humor y grotesco. “Los relámpagos desmitificadores” y otros ensayos críticos. Ana Rosa Domenella México, El Colegio de México / Universidad Autónoma Metropolitana Iztapalapa, 2011
La comunidad en cuestión. Un episodio de la historia moral del teatro, según Rousseau
Authors: De Mingo Rodríguez Alicia Ma.
Published: April 2018

El modelo de comunidad que diseña Rousseau, ya a partir de sus Discursos de la década de 1750, exigía que la propuesta ilustrada de D´Alembert para que hubiese un teatro estable en Ginebra fuese rechazada por Rousseau, con multitud de variados argumentos, en su Carta a D´Alembert sobre los espectáculos (1758), de una extraordinaria densidad historiográfica. Es necesario, sin embargo, no desatender lo esencial de la crítica de Rousseau, que él mismo embrolla, y situar la crítica al teatro en un terreno sobre todo simbólico, en tanto representa el arte sistemático de la simulación, la falsedad y el vivir disipadamente las vidas de otros, lo que apartaría a la persona y a la comunidad de la honestidad y sinceridad (autenticidad) que son imprescindibles a la transparencia como conditio sine qua non de la comunidad.
Analysis of Stresses Due to Traffic and Thermal Loads in Two-Lift Bonded Concrete Pavements by Finite Element Method
Authors: Swarna S. T. , Reddy K. S. , Reddy M. A. , Pandey B. B.
Published: April 2018

The current practice in the construction of jointed plain concrete pavements in India is to lay paving quality concrete (PQC) over roller-compacted concrete designated as dry lean concrete (DLC). A 125-µm plastic sheet is placed as a bond-breaking layer at the interface of the DLC and PQC. By placing the PQC layer directly over fresh lean concrete (LC), the two layers will bond without any extra bond-breaking layers, and there may be a considerable reduction in PQC thickness. Reducing the PQC layer thickness decreases the amount of aggregates used, which helps preserve quality aggregates that are rapidly depleting. Pavements in which the PQC is laid directly over LC can be designated as a two-lift concrete pavement (TLCP). Joints must be provided with deep saw cuts to avoid random cracking. The LC can be made up of recycled concrete or marginal aggregates to obtain a sustainable pavement. However, readymade analytical solutions are not available for the computation of stresses in two-lift bonded concrete layers for pavement design. This article presents a three-dimensional finite element solution for stresses in bonded concrete pavements. Stresses in both layers are presented in order to arrive at an optimum thickness combination so that both layers are safe during the design life. Stress computation is done for the conditions of simultaneous application of temperature gradients and axle loads. The cracking of the LC layer because of high flexural stresses at the bottom is found to be the critical factor in the design of TLCP.
Decision Support System for Management Decision in High-Risk Business Environment
Authors: Hsu Ming-Fu , Huang Chung-I
Published: April 2018

As a result of substantial variations in global financial markets, constructing an enterprise risk prewarning mechanism is essential. A vast amount of related studies have implemented monetary-related indicators to depict the full spectrum of an enterprise’s operating performance. Merely considering monetary-related indicators is unable to produce an in-depth understanding of an enterprise. To fill this gap, the balanced scorecard (BSC), with the advantages of being able to capture both monetary and nonmonetary indicators, was introduced. Unfortunately, the BSC also has its own challenges, one of which is the lack of consideration given to risk exposure, which affects an enterprise’s profit variation. Thus, this study extends the original BSC by considering risk exposure and introduces an artificial intelligence-based decision support system for management decision. The inherent decision logic embedded into neural network-based mechanisms is opaque and hard to comprehend by users. To handle the challenge, this study further incorporates fit theory with a knowledge visualization technique to handle the opaque nature of the model so as to decrease the cognitive load and mental burden. The empirical results show that the introduced model is a promising alternative for management decisions in highly fluctuating financial markets.
Mammalian BarH1Confers Commissural Neuron Identity on Dorsal Cells in the Spinal Cord
Authors: Saba Rie , Nakatsuji Norio , Saito Tetsuichiro
Published: April 2018

Commissural neurons in the spinal cord project their axons through the floor plate using a number of molecular interactions, such as netrins and their receptor DCC (deleted in colorectal cancer). However, the molecular cascades that control differentiation of commissural neurons are less characterized. A homeobox gene,MBH1(mammalian BarH1) was expressed specifically in a subset of dorsal cells in the developing spinal cord. Transgenic mice that carriedlacZandMBH1-flanking genome sequences demonstrated thatMBH1was expressed by commissural neurons. To analyze the function ofMBH1, we established anin vivoelectroporation method for the transfer of DNA into the mouse spinal cord. Ectopic expression ofMBH1drove dorsal cells into the fate of commissural neurons with concomitant expression of TAG-1 (transiently expressed axonal surface glycoprotein 1) and DCC. Cells ectopically expressingMBH1migrated to the deep dorsal horn, in which endogenousMBH1-positive cells accumulated. These results suggest thatMBH1functions upstream of TAG-1 and DCC and is involved in the fate determination of commissural neurons in the spinal cord.
GABAergic Control of Action Potential Propagation along Axonal Branches of Mammalian Sensory Neurons
Authors: Verdier Dorly , Lund James P. , Kolta Arlette
Published: April 2018

The main axons of mammalian sensory neurons are usually viewed as passive transmitters of sensory information. However, the spindle afferents of jaw-closing muscles behave as if action potential traffic along their central axons is phasically regulated during rhythmic jaw movements. In this paper, we used brainstem slices containing the cell bodies, stem axons, and central axons of these sensory afferents to show that GABA applied to the descending central (caudal) axon often abolished antidromic action potentials that were elicited by electrical stimulation of the tract containing the caudal axons of the recorded cells. This effect of GABA was most often not associated with a change in membrane potential of the soma and was still present in a calcium-free medium. It was mimicked by local applications of muscimol on the axons and was blocked by bath applications of picrotoxin, suggesting activation of GABAAreceptors located on the descending axon. Antidromic action potentials could also be blocked by electrical stimulation of local interneurons, and this effect was prevented by bath application of picrotoxin, suggesting that it results from the activation of GABAAreceptors after the release of endogenous GABA. We suggest that blockage is caused mainly by shunting within the caudal axon and that motor command circuits use this mechanism to disconnect the rostral and caudal compartments of the central axon, which allows the two parts of the neuron to perform different functions during movement.
Calcium Receptor-Induced Serotonin Secretion by Parafollicular Cells: Role of Phosphatidylinositol 3-Kinase-Dependent Signal Transduction Pathways
Authors: Liu Kuo-peing , Russo Andrew F. , Hsiung Shu-chi , Adlersberg Mella , Franke Thomas F. , Gershon Michael D. , Tamir Hadassah
Published: April 2018

Elevation of extracellular Ca2+(↑[Ca2+]e) stimulates the Ca2+receptor (CaR) to induce secretion of 5-hydroxytryptamine (5-HT) from the calcium-sensing parafollicular (PF) cells. The CaR has been reported to couple to Gαq with subsequent activation of protein kinase C-γ (PKCγ). We have identified a parallel transduction pathway in primary cultures of sheep PF cells by using a combinatorial approach in which we expressed adenoviral-encoded dominant-negative signaling proteins and performedin vitrokinase assays. The role of the CaR was established by expression of a dominant-negative CaR that eliminated calcium-induced 5-HT secretion but not secretion in response to KCl or phorbol esters. The calcium-induced secretion was inhibited by a dominant-negative p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K). PI3-K activity was also assayed using isoform-specific antibodies. The activity of p85/p110β (PI3-Kβ) immunocomplexes was elevated by ↑[Ca2+]eand activated by Gβγ subunits. In addition, secretion of 5-HT was antagonized by the expression of a minigene encoding a peptide scavenger of Gβγ subunits (C-terminal fragment peptide of bovine β-adrenergic receptor kinase). One target of PI3-K activity is phosphoinositide-dependent kinase-1 (PDK1), which in turn activated PKCζ. Expression of a dominant-negative PKCζ in PF cells reduced 5-HT secretion. Together, these observations establish that ↑[Ca2+]eevokes 5-HT secretion from PF cells by stimulating both Gαq- and Gβγ-signaling pathways downstream of the CaR. The βγ cascade subsequently activates PI3-Kβ-dependent signaling that is coupled to PDK1 and the downstream effector PKCζ, and results in an increase in 5-HT release.
Ischemic Insults Derepress the Gene Silencer REST in Neurons Destined to Die
Authors: Calderone Agata , Jover Teresa , Noh Kyung-min , Tanaka Hidenobu , Yokota Hidenori , Lin Ying , Grooms Sonja Y. , Regis Roodland , Bennett Michael V. L. , Zukin R. Suzanne
Published: April 2018

A subset of genes implicated in genetic and acquired neurological disorders encode proteins essential to neural patterning and neurogenesis. The gene silencing transcription factor neuronal repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) plays a critical role in elaboration of the neuronal phenotype. In neural progenitor and non-neural cells, REST acts by repression of a subset of neural genes important to synaptic plasticity and synaptic remodeling, including the AMPA receptor (AMPAR) subunit GluR2. Here we show that global ischemia triggers REST mRNA and protein expression. REST suppresses GluR2 promoter activity and gene expression in neurons destined to die. Because the GluR2 subunit governs AMPAR Ca2+permeability, these changes are expected to have profound effects on neuronal survival. In keeping with this concept, acute knockdown of the REST gene by antisense administration prevents GluR2 suppression and rescues post-ischemic neurons from ischemia-induced cell death in anin vitromodel. To our knowledge, our study represents the first example of ischemia-induced induction of a master transcriptional regulator gene and its protein expression critical to neural differentiation and patterning in adult neurons. Derepression of REST is likely to be an important mechanism of insult-induced neuronal death.
Adenylate Cyclase 1 as a Key Actor in the Refinement of Retinal Projection Maps
Authors: Ravary Anne , Muzerelle Aude , Hervé Denis , Pascoli Vincent , Ba-Charvet Kim Nguyen , Girault Jean-Antoine , Welker Egbert , Gaspar Patricia
Published: April 2018

cAMP occupies a strategic position to control neuronal responses to a large variety of developmental cues. We have analyzed the role of calcium-stimulated adenylate cyclase 1 (AC1) in the development of retinal topographic maps. AC1 is expressed in retinal ganglion cells (RGCs) from embryonic day 15 to adulthood with a peak during the first postnatal week. At that time, the other calcium-stimulated AC, AC8, is expressed in the superior colliculus (SC) but not in the RGCs. In mice of thebarrellessstrain, which carry an inactivating mutation of the AC1 gene, calcium-stimulated AC activity is reduced by 40–60% in the SC and retina. RGC projection maps were analyzed with a variety of anterograde and retrograde tracers. After an initially normal development until postnatal day 3, retinal fibers from the ipsilateral and contralateral eye fail to segregate into eye-specific domains in the lateral geniculate nucleus and the SC. Topographic defects in the fine tuning of the retinotectal and retinogeniculate maps are also observed with abnormalities in the confinement of the retinal axon arbors in the anteroposterior and mediolateral dimensions. This is attributable to the lack of elimination of misplaced axon collaterals and to the maintenance of a transient ipsilateral projection. These results establish an essential role of AC1 in the fine patterning of the retinal map. Calcium-modulated cAMP production in the RGCs could constitute an important link between activity-dependent changes and the anatomical restructuring of the retinal terminal arbors within central targets.
Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling
Authors: Rudhard York , Kneussel Matthias , Nassar Mohammed A. , Rast Georg F. , Annala Alexander J. , Chen Philip E. , Tigaret Cezar M. , Dean Isabel , Roes Juergen , Gibb Alasdair J. , Hunt Stephen P. , Schoepfer Ralf
Published: April 2018

Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+block might play a special role.

In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+insensitive and Ca2+impermeable.

Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NMDAR subunits and other important neurotransmitter receptors.

Our results show that coincidence detection by, and/or Ca2+permeability of, NMDARs is necessary for the development of somatotopic maps in the brainstem and suggest that highly specific signaling underlies synaptic refinement.
What Neural Correlates Underlie Successful Encoding and Retrieval? A Functional Magnetic Resonance Imaging Study Using a Divided Attention Paradigm
Authors: Kensinger Elizabeth A. , Clarke Richard J. , Corkin Suzanne
Published: April 2018

If attention is divided during learning, memory suffers. Nevertheless, individuals can learn information with divided attention. This event-related functional magnetic resonance imaging (fMRI) study (n= 17) investigated what neural processes support (1) learning with divided attention and (2) retrieval of information learned with divided attention. Participants encoded words (Is the word abstract or concrete?) while performing an auditory discrimination task (press a button whenever an auditory pattern changes). The auditory task was easy or hard, depending on the similarity of the patterns. A behavioral study indicated that detailed (“recollective”) information was more likely to be present for words encoded with the easy versus the hard concurrent task. Words encoded with the hard versus the easy concurrent task, in contrast, were more likely to rely on less detailed (“familiarity”-based) information. fMRI revealed encoding-related activation in the left prefrontal cortex (PFC) and left hippocampus that was linked to successful memory formation only for items encoded with the easy task. In contrast, activation in the right PFC and left parahippocampal gyrus was linked to successful memory for all items. Thus, successful encoding with the hard concurrent task was supported by a subset of the regions recruited for successful encoding with the easy task. The neural processes recruited for successful retrieval also depended on the encoding condition: The left PFC was disproportionately recruited for retrieval of items encoded with the easy task, whereas the right PFC was disproportionately recruited for retrieval of items encoded with the hard task. These findings may reflect left-sided specialization for recollective memories and right-sided specialization for familiarity-based traces.
Striatal Cell Type-Specific Overexpression of ΔFosB Enhances Incentive for Cocaine
Authors: Colby Christina R. , Whisler Kim , Steffen Cathy , Nestler Eric J. , Self David W.
Published: April 2018

The transcription factor ΔFosB accumulates in substance P–dynorphin-containing striatal neurons with repeated cocaine use. Here, we show that inducible transgenic ΔFosB overexpression in this same striatal cell type facilitates acquisition of cocaine self-administration at low-threshold doses, consistent with increased sensitivity to the pharmacological effects of the drug. Importantly, ΔFosB also enhances the degree of effort mice will exert to maintain self-administration of higher doses on a progressive ratio schedule of reinforcement, whereas levels of cocaine intake are not altered on less demanding fixed-ratio schedules. Acquisition and extinction of behavior reinforced by food pellets is not altered in ΔFosB-overexpressing mice, indicating that ΔFosB does not alter the capacity to learn an instrumental response or cause response perseveration in the absence of reinforcement. These data suggest that accumulation of ΔFosB contributes to drug addiction by increasing the incentive properties of cocaine, an effect that could increase the risk for relapse long after cocaine use ceases.
Respiratory Motor Recovery after Unilateral Spinal Cord Injury: Eliminating Crossed Phrenic Activity Decreases Tidal Volume and Increases Contralateral Respiratory Motor Output
Authors: Golder Francis J. , Fuller David D. , Davenport Paul W. , Johnson Richard D. , Reier Paul J. , Bolser Donald C.
Published: April 2018

By 2 months after unilateral cervical spinal cord injury (SCI), respiratory motor output resumes in the previously quiescent phrenic nerve. This activity is derived from bulbospinal pathways that cross the spinal midline caudal to the lesion (crossed phrenic pathways). To determine whether crossed phrenic pathways contribute to tidal volume in spinally injured rats, spontaneous breathing was measured in anesthetized C2hemisected rats at 2 months after injury with an intact ipsilateral phrenic nerve, or with ipsilateral phrenicotomy performed at the time of the SCI (i.e., crossed phrenic pathways rendered ineffective) (dual injury). Ipsilateral phrenicotomy did not alter the rapid shallow eupneic breathing pattern in C2injured rats. However, the ability to generate large inspiratory volumes after either vagotomy or during augmented breaths was impaired if crossed phrenic activity was abolished. We also investigated whether compensatory plasticity in contralateral motoneurons would be affected by eliminating crossed phrenic activity. Thus, contralateral phrenic motor output was recorded in anesthetized, vagotomized, and mechanically ventilated rats with dual injury during chemoreceptor stimulation. Hypercapnia, hypoxia, and asphyxia increased contralateral phrenic burst amplitude in the dual injury group more than in rats with SCI alone. Dual injury rats also had elevated baseline burst frequency. Together, these results demonstrate a functional role of crossed phrenic activity after SCI. Moreover, by preventing ipsilateral phrenic motor recovery in rats with unilateral SCI, segmental and supraspinal changes could be induced in contralateral respiratory motor output beyond that seen with SCI alone.
Spike Width Reduction Modifies the Dynamics of Short-Term Depression at a Central Synapse in the Locust
Authors: Niven J. E. , Burrows M.
Published: April 2018

Short-term synaptic depression is an important component of computation within neural networks, but little is known of its contribution to information processing during synaptically generated spike trains. We analyzed short-term synaptic depression at a synapse between two identified motoneurons innervating the hind leg of the locust: the FETi-FlTi synapse (fast extensor tibiae-flexor tibiae). Brief electrical stimulation of a single hind leg proprioceptor, the lump receptor (LR), led to prolonged sequences of spikes in FETi, similar in number and frequency to those during natural kicking movements. Depression at the FETi-FlTi synapse during LR-evoked spike bursts was compared quantitatively to that during antidromic spike trains evoked by electrical stimulation of FETi in the extensor tibiae muscle, and by modeling. The magnitude of the short-term depression was significantly greater during LR-evoked spike trains. On the basis of the model parameters required to fit the depression, the FETi-FlTi synapse is predominantly used for transmitting the timing of the onset of FETi spiking rather than its spike rate. During LR-evoked spike trains, there was a rapid reduction in presynaptic spike width that did not occur during antidromic spike trains under physiological calcium concentrations. This produced a concomitant reduction in the amplitude of the FlTi EPSP, suggesting that it contributed to the differences between the two stimulation regimes. Differences in the short-term depression between synaptically evoked and antidromic spike trains emphasize that the properties of synaptic information transfer are dependent on thein vivoconditions at the synapse and may not be reproduced byin vitrospike trains.
Anti-Inflammatory Drug Therapy Alters β-Amyloid Processing and Deposition in an Animal Model of Alzheimer's Disease
Authors: Yan Qiao , Zhang Jianhua , Liu Hantao , Babu-Khan Safura , Vassar Robert , Biere Anja Leona , Citron Martin , Landreth Gary
Published: April 2018

Alzheimer's disease (AD) is characterized by a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. Nonsteroidal anti-inflammatory drug (NSAID) treatment reduces AD risk, slows disease progression, and reduces microglial activation; however, the basis of these effects is unknown. We report that treatment of 11-month-old Tg2576 mice overexpressing human amyloid precursor protein (APP) with the NSAID ibuprofen for 16 weeks resulted in the dramatic and selective reduction of SDS-soluble β-amyloid (Aβ)42, whereas it had smaller effects on SDS-soluble Aβ40levels. Ibuprofen treatment resulted in 60% reduction of amyloid plaque load in the cortex of these animals.In vitrostudies using APP-expressing 293 cells showed that ibuprofen directly affected APP processing, specifically reducing the production of Aβ42. Ibuprofen treatment resulted in a significant reduction in microglial activation in the Tg2576 mice, as measured by CD45 and CD11b expression. NSAIDs activate the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ); however, a potent agonist of this receptor, pioglitazone, only modestly reduced SDS-soluble Aβ levels and did not affect amyloid plaque burden or microglia activation, indicating that PPARγ activation is not involved in the Aβ lowering effect of NSAIDs. These data show that chronic NSAID treatment can reduce brain Aβ levels, amyloid plaque burden, and microglial activation in an animal model of Alzheimer's disease.
Auditory Cortical Neurons Respond to Somatosensory Stimulation
Authors: Fu Kai-Ming G. , Johnston Taylor A. , Shah Ankoor S. , Arnold Lori , Smiley John , Hackett Troy A. , Garraghty Preston E. , Schroeder Charles E.
Published: April 2018

The prevailing hierarchical model of cortical sensory processing holds that early processing is specific to individual modalities and that combination of information from different modalities is deferred until higher-order stages of processing. In this paper, we present physiological evidence of multisensory convergence at an early stage of cortical auditory processing. We used multi-neuron cluster recordings, along with a limited sample of single-unit recordings, to determine whether neurons in the macaque auditory cortex respond to cutaneous stimulation. We found coextensive cutaneous and auditory responses in caudomedial auditory cortex, an area lying adjacent to A1, and at the second stage of the auditory cortical hierarchy. Somatosensory-auditory convergence in auditory cortex may underlie effects observed in human studies. Convergence of inputs from different sensory modalities at very early stages of cortical sensory processing has important implications for both our developing understanding of multisensory processing and established views of unisensory processing.
Group I Metabotropic Glutamate Receptors in the Monkey Striatum: Subsynaptic Association with Glutamatergic and Dopaminergic Afferents
Authors: Paquet Maryse , Smith Yoland
Published: April 2018

Group I metabotropic glutamate receptors (mGluRs) are involved in long-term synaptic plasticity and neuroprotection in the striatum, but the specific role(s) of mGluR1 and mGluR5 remain poorly understood. In this study, we used electron-microscopic immunocytochemistry to compare the pattern of subsynaptic and subcellular distribution of mGluR1a and mGluR5 in relation to putative glutamatergic and dopaminergic inputs to the monkey striatum.

At the light-microscopic level, both group I mGluRs are expressed in the striatal neuropil. In addition, numerous perikarya of striatal output neurons are immunostained for mGluR5, but much less frequently for mGluR1a. At the electron-microscopic level, immunoreactivity for both receptor subtypes is primarily expressed postsynaptically in dendrites and spines, although presynaptic mGluR1a labeling of glutamatergic thalamostriatal boutons and, less frequently, dopaminergic and corticostriatal terminals is also seen. In contrast to mGluR1a, mGluR5 immunoreactivity is rarely encountered presynaptically. In postsynaptic elements, 40-70% of immunoreactivity for both receptor subtypes is expressed intracellularly, whereas 30-60% is apposed to the plasma membrane. More than 80% of the labeling apposed to the plasma membrane is extrasynaptic. The remaining 20% is located at the edges of putative glutamatergic synapses or in the active zone of symmetric synapses. In mGluR5-, but not mGluR1a-immunostained sections, ∼70% of dopaminergic symmetric synapses are labeled perisynaptically.

These data emphasize the differential pattern of subsynaptic localization of the two group I mGluRs and provide various presynaptic and postsynaptic sites whereby mGluR1 and mGluR5 could mediate different, but complementary, effects on glutamatergic and dopaminergic transmission in the primate striatum.
Activity-Evoked Capacitative Ca2+Entry: Implications in Synaptic Plasticity
Authors: Baba Atsushi , Yasui Takuya , Fujisawa Shigeyoshi , Yamada Ryuji X. , Yamada Maki K. , Nishiyama Nobuyoshi , Matsuki Norio , Ikegaya Yuji
Published: April 2018

The Ca2+influx controlled by intracellular Ca2+stores, called store-operated Ca2+entry (SOC), occurs in various eukaryotic cells, but whether CNS neurons are endowed with SOC capability and how they may operate have been contentious issues. Using Ca2+imaging, we present evidence for the presence of SOC in cultured hippocampal pyramidal neurons. Depletion of internal Ca2+stores by thapsigargin caused intracellular Ca2+elevation, which was prevented by SOC channel inhibitors 2-aminoethoxydiphenyl borate (2-APB),SKF96365, and La3+. Interestingly, these inhibitors also accelerated the decay of NMDA-induced Ca2+transients without affecting their peak amplitude. In addition, SOC channel inhibitors attenuated tetanus-induced dendritic Ca2+accumulation and long-term potentiation at Schaffer collateral-CA1 synapses in hippocampal slice preparations. These data suggest a novel link between ionotropic receptor-activated SOC and neuroplasticity.
Cingulate Hypoactivity in Cocaine Users During a GO-NOGO Task as Revealed by Event-Related Functional Magnetic Resonance Imaging
Authors: Kaufman Jacqueline N. , Ross Thomas J. , Stein Elliot A. , Garavan Hugh
Published: April 2018

Although extensive evidence exists for the reinforcing properties of drugs of abuse such as cocaine, relatively less research has addressed the functional neuroanatomical correlates of the cognitive sequelae of these drugs. We present a functional magnetic resonance imaging study of a GO-NOGO task in which successful performance required prepotent behaviors to be inhibited. Significant cingulate, pre-supplementary motor and insula hypoactivity was observed for both successful NOGOs and errors of commission in chronic cocaine users relative to cocaine-naive controls. This attenuated response, in the presence of comparable activation levels in other task-related cortical areas, suggests cortical and psychological specificity in the locus of drug abuse-related cognitive dysfunction. The results suggest that addiction may be accompanied by a disruption of brain structures critical for the higher-order, cognitive control of behavior.
Activity of Different Classes of Neurons of the Motor Cortex during Postural Corrections
Authors: Beloozerova Irina N. , Sirota Mikhail G. , Swadlow Harvey A. , Orlovsky Grigori N. , Popova Lioudmila B. , Deliagina Tatiana G.
Published: April 2018

The dorsal side-up body orientation in quadrupeds is maintained by a postural system that is driven by sensory feedback signals. The spinal cord, brainstem, and cerebellum play essential roles in postural control, whereas the role of the forebrain is unclear. In the present study we investigated whether the motor cortex is involved in maintenance of the dorsal side-up body orientation. We recorded activity of neurons in the motor cortex in awake rabbits while animals maintained balance on a platform periodically tilting in the frontal plane. The tilts evoked postural corrections, i.e., extension of the limbs on the side moving down and flexion on the opposite side. Because of these limb movements, rabbits maintained body orientation close to the dorsal side up. Four classes of efferent neurons were studied: descending corticofugal neurons of layer V (CF5s), those of layer VI (CF6s), corticocortical neurons with ipsilateral projection (CCIs), and those with contralateral projection (CCCs). One class of inhibitory interneurons [suspected inhibitory neurons (SINs)] was also investigated. CF5 neurons and SINs were strongly active during postural corrections. In most of these neurons, a clear-cut modulation of discharge in the rhythm of tilting was observed. This finding suggests that the motor cortex is involved in postural control. In contrast to CF5 neurons, other classes of efferent neurons (CCI, CCC, CF6) were much less active during postural corrections. This suggests that corticocortical interactions, both within a hemisphere (mediated by CCIs) and between hemispheres (mediated by CCCs), as well as corticothalamic interactions via CF6 neurons are not essential for motor coordination during postural corrections.
Interaction between α-Melanocyte-Stimulating Hormone and Corticotropin-Releasing Hormone in the Regulation of Feeding and Hypothalamo-Pituitary-Adrenal Responses
Authors: Lu Xin-Yun , Barsh Gregory S. , Akil Huda , Watson Stanley J.
Published: April 2018

Both central α-melanocyte-stimulating hormone and corticotropin-releasing hormone (CRH) have been implicated in feeding and neuroendocrine mechanisms. The anatomical overlap and functional similarities between these two neurotransmitter systems led to the hypothesis that CRH might act as one of the mediators of the central actions of the melanocortin system. By double-labelingin situhybridization, a subpopulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN) were shown to contain the melanocortin-4 receptor (MC4R), concentrated in the ventromedial part of the parvicellular PVN (up to 33%). Intracerebroventricular injection of melanocortin agonist MTII to conscious and freely moving rats induced a rapid induction of CRH gene transcription in the PVN. This effect was accompanied by a rise in plasma corticosterone levels in a dose- and time-dependent manner, with the maximum response observed 30 min after MTII injection. MTII (0.5 nmol)-induced increase in plasma corticosterone was attenuated by the selective MC4R antagonist HS014 (0.25-1.0 nmol) and nonselective CRH receptor antagonist α-helical-CRH9-41(0.125-0.5 nmol) in a dose-dependent manner. Moreover, the anorectic effect of MTII was evaluated at 1, 2, and 24 hr after intracerebroventricular injection. Approximately half of the inhibitory effect of MTII (0.5 nmol) on food intake was reversed by pretreatment withα-helical-CRH9-41at 0.25 and 0.5 nmol doses. Collectively, these results provide evidence that CRH acts as a downstream mediator of melanocortin signaling and contributes to the mechanisms by which the central melanocortin system controls feeding and neuroendocrine responses.
Comparison ofHermissendaType A and Type B Photoreceptors: Response to Light as a Function of Intensity and Duration
Authors: Mo Ji Ling , Blackwell Kim T.
Published: April 2018

Hermissenda crassicornisis an invertebrate model used to study classical conditioning using light as the conditioned stimulus. The memory of the association is stored in type B photoreceptors, the output of which depends on interactions with type A photoreceptors. To understand the effect of classical conditioning on the output of type B photoreceptors in response to light, we measured the effect of light duration and intensity on membrane potential in both photoreceptor types ofHermissenda. The results show that, independent of light stimulus, the afterhyperpolarization is significantly greater in type A than in type B photoreceptors. In response to light, the generator potential (GP) rises linearly with an increase in either intensity or duration for both type A and type B photoreceptors. However, the difference between type A and type B photoreceptors depends on the time after light onset; the increase in peak GP with intensity is steeper in type A than type B, but by 14 sec after light onset, membrane potential is greater in type B than type A photoreceptors. Similarly, firing frequency increases with intensity and duration in both photoreceptor types but with a difference that is time dependent. During the first second after light onset, type A photoreceptors have a significantly higher firing frequency than type B photoreceptors; after this time, firing frequency is higher in type B than type A photoreceptors. Although membrane potential is correlated with firing frequency, this correlation is much lower in type A than type B photoreceptors, suggesting that some other conductance influences firing frequency in type A photoreceptors.
Glycine Receptor Knock-In Mice and Hyperekplexia-Like Phenotypes: Comparisons with the Null Mutant
Authors: Findlay Geoffrey S. , Phelan Rachel , Roberts Michael T. , Homanics Gregg E. , Bergeson Susan E. , Lopreato Gregory F. , Mihic S. John , Blednov Yuri A. , Harris R. Adron
Published: April 2018

Strychnine-sensitive glycine receptors (GlyRs) inhibit neurotransmission in the spinal cord and brainstem. To better define the function of this receptorin vivo, we constructed a point mutation that impairs receptor function in the α1-subunit and compared these knock-in mice tooscillator(spdot) mice lacking functional GlyR α1-subunits. Mutation of the serine residue at amino acid 267 to glutamine (α1S267Q) results in a GlyR with normal glycine potency but decreased maximal currents, as shown by electrophysiological recordings usingXenopusoocytes. In addition, single-channel recordings using human embryonic kidney 293 cells indicated profoundly altered properties of the mutated GlyR. We produced knock-in mice bearing the GlyR α1S267Q mutation to assess thein vivoconsequences of selectively decreasing GlyR efficacy. Chloride uptake into brain synaptoneurosomes from knock-in mice revealed decreased responses to maximally effective glycine concentrations, although wild-type levels of GlyR expression were observed using3H-strychnine binding and immunoblotting. A profound increase in the acoustic startle response was observed in knock-in mice as well as a “limb clenching” phenotype. In contrast, no changes in coordination or pain perception were observed using the rotarod or hot-plate tests, and there was no change in GABAA-receptor-mediated chloride uptake. Homozygous S267Q knock-in mice, like homozygousspdotmice, exhibited seizures and died within 3 weeks of birth. In heterozygousspdotmice, both decreased3H-strychnine binding and chloride flux were observed; however, neither enhanced acoustic startle responses nor limb clenching were seen. These data demonstrate that a dominant-negative point mutation in GlyR disrupting normal function can produce a more dramatic phenotype than the corresponding recessive null mutation, and provides a new animal model to evaluate GlyR functionin vivo.
Genetic and Cellular Basis for Acetylcholine Inhibition ofCaenorhabditis elegansEgg-Laying Behavior
Authors: Bany I. Amy , Dong Meng-Qiu , Koelle Michael R.
Published: April 2018

Egg-laying behavior inCaenorhabditis elegansis activated by signaling through the G-protein Gρqand inhibited by signaling through a second G-protein, Gρo. Activation of egg laying depends on the serotonergic hermaphrodite-specific neurons (HSNs), but the neurotransmitter(s) and cell(s) that signal to inhibit egg laying are not known. Mutants for G-protein signaling genes have well characterized defects in egg laying. Here we present an analysis of mutants for other genes reported to lack inhibition of egg laying. Of the nine strongest, six have morphological defects in the ventral-type C (VC) neurons, which synapse onto both the HSNs and the egg-laying muscles and are thus the third cell type comprising the egg-laying system. Laser-ablating VC neurons could also disrupt the inhibition of egg laying. The remaining three mutants (unc-4, cha-1, andunc-17) are defective for synthesis or packaging of acetylcholine in the VCs. The egg-laying defects ofunc-4, cha-1,andunc-17were rescued by VC-specific expression of the corresponding cDNAs. In addition, increasing synaptic acetylcholine by reducing acetylcholinesterase activity, with either mutations or the inhibitor aldicarb, decreased egg laying. Finally, we found that a knock-out for the HSN-expressed receptor G-protein-coupled acetylcholine receptor 2 (GAR-2) shows a partial defect in the inhibition of egg laying and fails to respond to aldicarb. Our results show that acetylcholine released from the VC neurons inhibits egg-laying behavior. This inhibition may be caused, in part, by acetylcholine signaling onto the HSN presynaptic terminals, via GAR-2, to inhibit neurotransmitter release.
Brain-Derived Neurotrophic Factor Activation of NFAT (Nuclear Factor of Activated T-Cells)-Dependent Transcription: A Role for the Transcription Factor NFATc4 in Neurotrophin-Mediated Gene Expression
Authors: Groth Rachel D. , Mermelstein Paul G.
Published: April 2018

A member of the neurotrophin family, brain-derived neurotrophic factor (BDNF) regulates neuronal survival and differentiation during development. Within the adult brain, BDNF is also important in neuronal adaptive processes, such as the activity-dependent plasticity that underlies learning and memory. These long-term changes in synaptic strength are mediated through alterations in gene expression. However, many of the mechanisms by which BDNF is linked to transcriptional and translational regulation remain unknown. Recently, the transcription factor NFATc4 (nuclear factor of activated T-cells isoform 4) was discovered in neurons, where it is believed to play an important role in long-term changes in neuronal function. Interestingly, NFATc4 is particularly sensitive to the second messenger systems activated by BDNF. Thus, we hypothesized that NFAT-dependent transcription may be an important mediator of BDNF-induced plasticity. In cultured rat CA3-CA1 hippocampal neurons, BDNF activated NFAT-dependent transcription via TrkB receptors. Inhibition of calcineurin blocked BDNF-induced nuclear translocation of NFATc4, thus preventing transcription. Further, phospholipase C was a critical signaling intermediate between BDNF activation of TrkB and the initiation of NFAT-dependent transcription. Both inositol 1,4,5-triphosphate (IP3)-mediated release of calcium from intracellular stores and activation of protein kinase C were required for BDNF-induced NFAT-dependent transcription. Finally, increased expression of IP3receptor 1 and BDNF after neuronal exposure to BDNF was linked to NFAT-dependent transcription. These results suggest that NFATc4 plays a crucial role in neurotrophin-mediated synaptic plasticity.
GABA Is Involved in Spatial Unmasking in the Frog Auditory Midbrain
Authors: Lin Wen-Yu , Feng Albert S.
Published: April 2018

Real-world listening situations comprise multiple auditory objects. Sounds originating from different objects are summated at the eardrum. The auditory system therefore must segregate the streams of sounds associated with the different objects. One listening strategy in complex environments is to attend to signals originating from one spatial location. In doing so, signal detection is compromised when a masker is present at close proximity, and detection is improved if the masker is spatially separated from the signal. A recent study has shown that, in frogs, spatial unmasking is more robust at the midbrain than at the periphery, indicating the importance of central mechanisms for this process. In this study, we investigated spatial unmasking patterns of single neurons in the frog inferior colliculus (IC) before and during iontophoretic application of bicuculline, a GABAAreceptor antagonist. We found that drug application markedly decreased the strength of spatial unmasking such that even large angular separation of signal and masker sources produced only a weak masking release. Under the drug, the strength of spatial unmasking of midbrain neurons approximated that of auditory nerve fibers. These data show that GABAergic interactions in the auditory midbrain play an important role in spatial unmasking. Analysis of the effect of the drug on the direction sensitivity of the units shows that for the majority of IC units, bicuculline degrades binaural processing involved in directional coding, thereby compromising spatial unmasking. For other IC units, however, the decline in the strength of spatial unmasking is attributable to the effects of bicuculline on different central auditory processes.
Slit2 Guides Both Precrossing and Postcrossing Callosal Axons at the MidlineIn Vivo
Authors: Shu Tianzhi , Sundaresan Vasi , McCarthy Margaret M. , Richards Linda J.
Published: April 2018

Commissural axons generally cross the midline only once. In theDrosophilanerve cord and mouse spinal cord, commissural axons are guided by Slit only after they cross the midline, where Slit prevents these axons from recrossing the midline. In the developing corpus callosum, Slit2 expressed by the glial wedge guides callosal axons before they cross the midline, as they approach the corticoseptal boundary. These data highlighted a potential difference between the role of Slit2 in guiding commissural axons in the brain compared with the spinal cord. Here, we investigate whether Slit2 also guides callosal axons after they cross the midline. Because such questions cannot be addressed in conventional gene knock-out animals, we usedin uteroinjections of antisense oligonucleotides to specifically deplete Slit2 on only one side of the brain. We used this technique together with a novelin vitroassay of hemisected brain slices to specifically analyze postcrossing callosal axons. We find that in the brain, unlike the spinal cord, Slit2 mediates both precrossing and postcrossing axonal guidance. Depletion of Slit2 on one side of the brain causes axons to defasciculate and, in some cases, to aberrantly enter the septum. Because these axons do not recross the midline, we conclude that the principle function of Slit2 at the cortical midline may be to channel the axons along the correct path and possibly repel them away from the midline. We find no evidence that Slit2 prevents axons from recrossing the midline in the brain.