Bank Borrowing and Financing of Medium-sized Firms in Indonesia

The improvement of financial intermediation functions is crucial for a robust banking system. When lending, banks have to cope with such problems as information asymmetry and adverse selection. In order to mitigate these problems, banks have to product information and improve their techniques of lending. During the 1998 financial crisis, Indonesia's banking system suffered severe damage and revealed that the country's banking intermediation functions did not work well. This paper examines the financial intermediation functions of banks in Indonesia and analyzes the importance of bank lending to firms. The focus is on medium-sized firms, and "relationship lending", one of the bank lending techniques, is used to examine financial intermediation in Indonesia. The results of logit regressions show that the relationship between a bank and a firm affects the probability of bank lending. The amount of borrowing and collateral are also affected by a firm's relationship with a bank. When viewed from the standpoint of relationship lending to medium-sized firms, Indonesian banks cannot be criticized for any malfunction of financial intermediation.

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.

Evaluación de los co-beneficios sobre el desarrollo sostenible y la reducción de la pobreza de proyectos de mitigación del cambio climático en Brasil

El cambio climático y los diferentes aspectos del concepto de “desarrollo” están intrínsecamente interconectados. Por un lado, el desarrollo económico de nuestras sociedades ha contribuido a un aumento insostenible de las emisiones de gases de efecto invernadero, las cuales están desestabilizando el sistema climático global, generando al mismo tiempo una distribución desigual de la capacidad de las personas para hacer frente a estos cambios. Por otro lado, en la actualidad existe un amplio consenso sobre que el cambio climático impacta directamente y de manera negativa sobre el denominando desarrollo sostenible. De igual manera, cada vez existe un mayor consenso de que el cambio climático va a desafiar sustancialmente nuestra capacidad de erradicar la pobreza a medio y largo plazo. Ante esta realidad, no cabe duda de que las estrategias de adaptación son esenciales para mantener el desarrollo. Es por esto que hasta el momento, los mayores esfuerzos realizados por unir las agendas globales de la lucha contra la pobreza y del cambio climático se han dado en el entorno de la adaptación al cambio climático. Sin embargo, cada vez son más los actores que defienden, desde distintos escenarios, que existen sinergias entre la mitigación de emisiones y la mejora de las condiciones de vida de las poblaciones más vulnerables, favoreciendo así un “desarrollo sostenible” sin disminuir los recursos financieros destinados a la adaptación. Para hacer efectivo este potencial, es imprescindible identificar diseños de estrategias de mitigación que incrementen los resultados de desarrollo, contribuyendo al desarrollo sostenible al mismo tiempo que a reducir la pobreza. En este contexto se sitúa el objetivo principal de esta investigación, consistente en analizar los co-beneficios locales, para el desarrollo sostenible y la reducción la pobreza, de proyectos de mitigación del cambio climático que se implementan en Brasil. Por co-beneficios se entienden, en el lenguaje de las discusiones internacionales de cambio climático, aquellos beneficios que van más allá de la reducción de emisiones de Gases de Efecto Invernadero (GEI) intrínsecas por definición a los proyectos de mitigación. Los proyectos de mitigación más relevantes hasta el momento bajo el paraguas de la Convención Marco de las Naciones Unidas para el Cambio Climático (CMNUCC), son los denominados Mecanismos de Desarrollo Limpio (MDL) del Protocolo de Kioto. Sin embargo, existen alternativas de proyectos de mitigación (tales como los denominados “estándares adicionales” a los MDL de los Mercados Voluntarios de Carbono y las Tecnologías Sociales), que también serán tenidos en cuenta en el marco de este estudio. La elección del tema se justifica por la relevancia del mismo en un momento histórico en el que se está decidiendo el futuro del régimen climático a partir del año 2020. Aunque en el momento de redactar este documento, todavía no se ha acordado la forma que tendrán los futuros instrumentos de mitigación, sí que se sabe que los co-beneficios de estos instrumentos serán tan importantes, o incluso más, que las reducciones de GEI que generan. Esto se debe, principalmente, a las presiones realizadas en las negociaciones climáticas por parte de los países menos desarrollados, para los cuales el mayor incentivo de formar parte de dichas negociaciones se basa principalmente en estos potenciales co-beneficios. Los resultados de la tesis se estructuran alrededor de tres preguntas de investigación: ¿cómo están contribuyendo los MDL implementados en Brasil a generar co-beneficios que fomenten el desarrollo sostenible y reduzcan la pobreza?; ¿existen proyectos de mitigación en Brasil que por tener compromisos más exigentes en cuanto a su contribución al desarrollo sostenible y/o la reducción de la pobreza que los MDL estén siendo más eficientes que estos en relación a los co-beneficios que generan?; y ¿qué características de los proyectos de mitigación pueden resultar críticas para potenciar sus co-beneficios en las comunidades en las que se implementan? Para dar respuesta a estas preguntas, se ha desarrollado durante cuatro años una labor de investigación estructurada en varias fases y en la que se combinan diversas metodologías, que abarcan desde el desarrollo de un modelo de análisis de cobeneficios, hasta la aplicación del mismo tanto a nivel documental sobre 194 documentos de diseño de proyecto (denominado análisis ex-ante), como a través de 20 casos de estudio (denominado análisis ex-post). Con la realización de esta investigación, se ha confirmado que los requisitos existentes hasta el momento para registrar un proyecto como MDL bajo la CMNUCC no favorecen sustancialmente la generación de co-beneficios locales para las comunidades en las que se implementan. Adicionalmente, se han identificado prácticas y factores, que vinculadas a las actividades intrínsecas de los proyectos de mitigación, son efectivas para incrementar sus co-beneficios. Estas prácticas y factores podrán ser tenidas en cuenta tanto para mejorar los requisitos de los actuales proyectos MDL, como para apoyar la definición de los nuevos instrumentos climáticos. ABSTRACT Climate change and development are inextricably linked. On the one hand, the economic development of our societies has contributed to the unsustainable increase of Green House Gases emissions, which are destabilizing the global climate system while fostering an unequal distribution of people´s ability to cope with these changes. On the other hand, there is now a consensus that climate change directly impacts the so-called sustainable development. Likely, there is a growing agreement that climate change will substantially threaten our capacity to eradicate poverty in the medium and long term. Given this reality, there is no doubt that adaptation strategies are essentials to keep development. This is why, to date, much of the focus on poverty in the context of climate change has been on adaptation However, without diverting resources from adaptation, there may exist the potential to synergize efforts to mitigate emissions, contribute to sustainable development and reduce poverty. To fulfil this potential, it is key identifying how mitigation strategies can also support sustainable development and reduce poverty. In this context, the main purpose of this investigation is to explore the co-benefits, for sustainable development and for poverty reduction, of climate change mitigation projects being implemented in Brazil. In recent years the term co-benefits, has been used by policy makers and academics to refer the potentially large and diverse range of collateral benefits that can be associated with climate change mitigation policies in addition to the direct avoided climate impact benefits. The most relevant mitigation projects developed during the last years under the United Nations Framework Convention on Climate Change (UNFCCC) are the so-called Clean Development Mechanisms (CDM) of the Kyoto Protocol. Thus, this research will analyse this official mechanism. However, there are alternatives to the mitigation projects (such as the "add-on standards" of the Voluntary Carbon Markets, and the Social Technologies) that will also be assessed as part of the research. The selection of this research theme is justified because its relevance in a historic moment in which proposals for a future climate regime after 2020 are being negotiated. Although at the moment of writing this document, there is not a common understanding on the shape of the new mitigation instruments, there is a great agreement about the importance of the co-benefits of such instruments, which may be even more important for the Least Developed Countries that their expected greenhouse gases emissions reductions. The results of the thesis are structured around three research questions: how are the CDM projects being implemented in Brazil generating local co-benefits that foster sustainable development and poverty reduction?; are other mitigation projects in Brazil that due to their more stringent sustainable development and/o poverty reduction criteria, any more successful at delivering co-benefits than regular CDM projects?; and what are the distinguishing characteristics of mitigation projects that are successful at delivering co-benefits? To answer these research questions, during four years it has been developed a research work structured in several phases and combining various methodologies. Those methodologies cover from the development of a co-benefits assessment model, to the application of such model both to a desktop analysis of 194 project design documents, and to 20 case studies using field data based on site visits to the project sites. With the completion of this research, it has been confirmed that current requirements to register a CDM project under the UNFCCC not substantially favour co-benefits at the local level. In addition, some practices and factors enablers of co-benefits have been identified. These characteristics may be taken into consideration to improve the current CDM and to support the definition of the new international market mechanisms for climate mitigation.

Combine use of Selected Schizosaccharomyces pombe and Lachancea thermotolerans Yeast Strains as an Alternative to the Traditional Malolactic Fermentation in Red Wine Production

Most red wines commercialized in the market use the malolactic fermentationprocess in order to ensure stability from a microbiological point of view. In this secondfermentation, malic acid is converted into L-lactic acid under controlled setups. Howeverthis process is not free from possible collateral effects that on some occasions produceoff-flavors, wine quality loss and human health problems. In warm viticulture regions suchas the south of Spain, the risk of suffering a deviation during the malolactic fermentationprocess increases due to the high must pH. This contributes to produce wines with highvolatile acidity and biogenic amine values. This manuscript develops a new red winemakingmethodology that consists of combining the use of two non-Saccharomyces yeast strains asan alternative to the traditional malolactic fermentation. In this method, malic acid is totallyconsumed by Schizosaccharomyces pombe, thus achieving the microbiological stabilizationobjective, while Lachancea thermotolerans produces lactic acid in order not to reduce andeven increase the acidity of wines produced from low acidity musts. This technique reducesthe risks inherent to the malolactic fermentation process when performed in warm regions.The result is more fruity wines that contain less acetic acid and biogenic amines than thetraditional controls that have undergone the classical malolactic fermentation.

A methodology proposal to obtain operational parameter forecasts and operational risk assessment in container terminals

Las terminales de contenedores son sistemas complejos en los que un elevado número de actores económicos interactúan para ofrecer servicios de alta calidad bajo una estricta planificación y objetivos económicos. Las conocidas como "terminales de nueva generación" están diseñadas para prestar servicio a los mega-buques, que requieren tasas de productividad que alcanzan los 300 movimientos/ hora. Estas terminales han de satisfacer altos estándares dado que la competitividad entre terminales es elevada. Asegurar la fiabilidad de las planificaciones del atraque es clave para atraer clientes, así como reducir al mínimo el tiempo que el buque permanece en el puerto. La planificación de las operaciones es más compleja que antaño, y las tolerancias para posibles errores, menores. En este contexto, las interrupciones operativas deben reducirse al mínimo. Las principales causas de dichas perturbaciones operacionales, y por lo tanto de incertidumbre, se identifican y caracterizan en esta investigación. Existen una serie de factores que al interactuar con la infraestructura y/o las operaciones desencadenan modos de fallo o parada operativa. Los primeros pueden derivar no solo en retrasos en el servicio sino que además puede tener efectos colaterales sobre la reputación de la terminal, o incluso gasto de tiempo de gestión, todo lo cual supone un impacto para la terminal. En el futuro inmediato, la monitorización de las variables operativas presenta gran potencial de cara a mejorar cualitativamente la gestión de las operaciones y los modelos de planificación de las terminales, cuyo nivel de automatización va en aumento. La combinación del criterio experto con instrumentos que proporcionen datos a corto y largo plazo es fundamental para el desarrollo de herramientas que ayuden en la toma de decisiones, ya que de este modo estarán adaptadas a las auténticas condiciones climáticas y operativas que existen en cada emplazamiento. Para el corto plazo se propone una metodología con la que obtener predicciones de parámetros operativos en terminales de contenedores. Adicionalmente se ha desarrollado un caso de estudio en el que se aplica el modelo propuesto para obtener predicciones de la productividad del buque. Este trabajo se ha basado íntegramente en datos proporcionados por una terminal semi-automatizada española. Por otro lado, se analiza cómo gestionar, evaluar y mitigar el efecto de las interrupciones operativas a largo plazo a través de la evaluación del riesgo, una forma interesante de evaluar el effecto que eventos inciertos pero probables pueden generar sobre la productividad a largo plazo de la terminal. Además se propone una definición de riesgo operativo junto con una discusión de los términos que representan con mayor fidelidad la naturaleza de las actividades y finalmente, se proporcionan directrices para gestionar los resultados obtenidos. Container terminals are complex systems where a large number of factors and stakeholders interact to provide high-quality services under rigid planning schedules and economic objectives. The socalled next generation terminals are conceived to serve the new mega-vessels, which are demanding productivity rates up to 300 moves/hour. These terminals need to satisfy high standards because competition among terminals is fierce. Ensuring reliability in berth scheduling is key to attract clients, as well as to reduce at a minimum the time that vessels stay the port. Because of the aforementioned, operations planning is becoming more complex, and the tolerances for errors are smaller. In this context, operational disturbances must be reduced at a minimum. The main sources of operational disruptions and thus, of uncertainty, are identified and characterized in this study. External drivers interact with the infrastructure and/or the activities resulting in failure or stoppage modes. The later may derive not only in operational delays but in collateral and reputation damage or loss of time (especially management times), all what implies an impact for the terminal. In the near future, the monitoring of operational variables has great potential to make a qualitative improvement in the operations management and planning models of terminals that use increasing levels of automation. The combination of expert criteria with instruments that provide short- and long-run data is fundamental for the development of tools to guide decision-making, since they will be adapted to the real climatic and operational conditions that exist on site. For the short-term a method to obtain operational parameter forecasts in container terminals. To this end, a case study is presented, in which forecasts of vessel performance are obtained. This research has been entirely been based on data gathered from a semi-automated container terminal from Spain. In the other hand it is analyzed how to manage, evaluate and mitigate disruptions in the long-term by means of the risk assessment, an interesting approach to evaluate the effect of uncertain but likely events on the long-term throughput of the terminal. In addition, a definition for operational risk evaluation in port facilities is proposed along with a discussion of the terms that better represent the nature of the activities involved and finally, guidelines to manage the results obtained are provided.

Calibration of accelerometers for the measurement of microvibrations

The accelerometers used for the measurement of microvibrations or microgravity applications, such as active control of space structures, attitude control, scientific payloads, or even on-Earth testing of structures at very low-excitation levels, require a dedicated calibration procedure that includes the gravitational effects. Otherwise, on-Earth calibrations can be inaccurate due to the collateral projection of the local gravity onto the sensitive axis. An on-Earth calibration technique for the 107102s amplitude range and 0-100-Hz frequency range is described. Special attention has been given to the modeling of gravitational effects on the response of the calibration device and the accelerometer itself. The sensitivity and resolution tests performed on piezoelectric accelerometers showthe accuracy andthe potential of thistechnique. Typical scale factorun certainty, which hasbeen carefully analyzed, is of the order of 2% at acceleration levels of 10sg.

ANÁLISE DAS MUDANÇAS DOS FATORES DETERMINANTES DA ESTRUTURA DE CAPITAL EM FUNÇÃO DO CICLO DE VIDA DAS EMPRESAS BRASILEIRAS

As várias teorias acerca da estrutura de capital despertam interesse motivando diversos estudos sobre o assunto sem, no entanto, ter um consenso. Outro tema aparentemente pouco explorado refere-se ao ciclo de vida das empresas e como ele pode influenciar a estrutura de capital. Este estudo teve como objetivo verificar quais determinantes possuem maior relevância no endividamento das empresas e se estes determinantes alteram-se dependendo do ciclo de vida da empresa apoiada pelas teorias Trade Off, Pecking Order e Teoria da Agência. Para alcançar o objetivo deste trabalho foi utilizado análise em painel de efeito fixo sendo a amostra composta por empresas brasileiras de capital aberto, com dados secundários disponíveis na Economática® no período de 2005 a 2013, utilizando-se os setores da BM&FBOVESPA. Como resultado principal destaca-se o mesmo comportamento entre a amostra geral, alto e baixo crescimento pelo endividamento contábil para o determinante Lucratividade apresentando uma relação negativa, e para os determinantes Oportunidade de Crescimento e Tamanho, estes com uma relação positiva. Para os grupos de alto e baixo crescimento alguns determinantes apresentaram resultados diferentes, como a singularidade que resultou significância nestes dois grupos, sendo positiva no baixo crescimento e negativa no alto crescimento, para o valor colateral dos ativos e benefício fiscal não dívida apresentaram significância apenas no grupo de baixo crescimento. Para o endividamento a valor de mercado foi observado significância para o Benefício fiscal não dívida e Singularidade. Este resultado reforça o argumento de que o ciclo de vida influência a estrutura de capital.

O DISCURSO DE HUMANIZAÇÃO COMO ESTRATÉGIA DE APROXIMAÇÃO COM O CONSUMIDOR NAS PUBLICIDADES DAS MÍDIAS SOCIAIS

Este trabalho propõe o estudo analítico de estratégias discursivas das organizações empregadas nas publicidades das mídias sociais no Brasil em que, na tentativa de aproximação com os consumidores, as empresas emitem discursos de humanização. A pesquisa ocupou-se em identificar e analisar as publicidades das marcas notabilizadas nesse ambiente superabundante de informação, capazes de comunicar-se efetivamente com os consumidores, a ponto de levá-los ao engajamento com os interesses da organização pela interação e compartilhamento dos conteúdos nas mídias sociais, e de torná-los os agentes da marca, aqueles que divulgam voluntariamente os seus benefícios para a sua rede de amigos. Trata-se de uma pesquisa exploratória de teor qualitativo, cuja busca se dará pelas delineações de um espaço discursivo. Utilizou-se a análise do discurso (AD), da linha francesa, sob a perspectiva dos estudos do ethos, cenas de enunciação e contrato de comunicação que contemplam os discursos organizacionais. Além da conceituação teórica e revisão de literatura vinculadas às mídias sociais e cultura organizacional, o trabalho analisou as publicidades em vídeo publicadas no Facebook e YouTube, nos anos de 2014 e 2015, cujo intuito era a aproximação com o consumidor. A pesquisa demonstrou que o ambiente das mídias sociais requer outra postura das organizações, uma linguagem dialógica e interativa com a participação do consumidor nas suas publicidades. A supervalorização do consumidor e a sua inclusão nas narrativas é uma tentativa de humanizar as relações entre organização e seus públicos e demonstram ser o eixo conciliador entre ambos na nova ambiência midiática.

Cooperative interactions in the induction of long-term potentiation and depression of synaptic excitation between hippocampal CA3-CA1 cell pairs in vitro.

The requirement for cooperative interactions between multiple synaptic inputs in the induction of long-term potentiation (LTP) and long-term depression (LTD) has been tested at Schaffer collateral synapses with paired recordings from monosynaptically coupled CA3-CA1 cell pairs in rat hippocampal slice cultures. Tetanization of single presynaptic neurons at 50 Hz (repeated 5-7 times for 300-500 ms each) induced only a transient potentiation (< 3 min) of excitatory postsynaptic potentials (EPSPs). Persistent potentiation (> 15 min) was induced only when single presynaptic action potentials were synchronously paired with directly induced postsynaptic depolarizing pulses (repeated 50-100 times). Tetanus-induced potentiation of extracellularly evoked EPSPs lasting > 4 min could only be obtained if the EPSP was > 4 mV. Because unitary EPSP amplitudes average approximately 1 mV, we conclude that high-frequency discharge must occur synchronously] in 4-5 CA3 cells for LTP to be induced in a common postsynaptic CA1 cell. Asynchronous pairing of presynaptic action potentials with postsynaptic depolarizing current pulses (preceding each EPSP by 800 ms) depressed both naive and previously potentiated unitary EPSPs. Likewise, homosynaptic LTD of unitary EPSPs was induced when the presynaptic cell was tetanized at 3 Hz for 3 min, regardless of their amplitude (0.3-3.2 mV). Homosynaptic LTD of extracellularly evoked Schaffer collateral EPSPs < 4 mV could be induced if no inhibitory postsynaptic potential was apparent, but was prevented by eliciting a large inhibitory postsynaptic potential or by injection of hyperpolarizing current in the postsynaptic cell. We conclude that cooperative interactions among multiple excitatory inputs are not required for induction of homosynaptic LTD of unitary EPSPs.

Reconstitution of the hippocampal mossy fiber and associational-commissural pathways in a novel dissociated cell culture system.

Synapses of the hippocampal mossy fiber pathway exhibit several characteristic features, including a unique form of long-term potentiation that does not require activation of the N-methyl-D-aspartate receptor by glutamate, a complex postsynaptic architecture, and sprouting in response to seizures. However, these connections have proven difficult to study in hippocampal slices because of their relative paucity (<0.4%) compared to commissural-collateral synapses. To overcome this problem, we have developed a novel dissociated cell culture system in which we have enriched mossy fiber synapses by increasing the ratio of granule-to-pyramidal cells. As in vivo, mossy fiber connections are composed of large dynorphin A-positive varicosities contacting complex spines (but without a restricted localization). The elementary synaptic connections are glutamatergic, inhibited by dynorphin A, and exhibit N-methyl-D-aspartate-independent long-term potentiation. Thus, the simplicity and experimental accessibility of this enriched in vitro mossy fiber pathway provides a new perspective for studying nonassociative plasticity in the mammalian central nervous system.

A presynaptic locus for long-term potentiation of elementary synaptic transmission at mossy fiber synapses in culture.

The complex circuitry of the CA3 region and the abundance of collateral connections has made it difficult to study the mossy fiber pathway in hippocampal slices and therefore to establish the site of expression of long-term potentiation at these synapses. Using a novel cell culture system, we have produced long-term potentiation of the elementary synaptic connections on single CA3 pyramidal neurons following tetanic stimulation of individual dentate gyrus granule cells. As is the case for the hippocampal slice, this potentiation was independent of N-methyl-D-aspartate receptor activation, was simulated by application of forskolin, and its induction did not require any modulatory input. The increase in synaptic strength was accompanied by a reduction in the number of failures of transmission and by an increase in the coefficient of variation of the responses and was prevented by presynaptic injection of an inhibitor of protein kinase A. These findings show that mossy fiber long-term potentiation has a presynaptic locus and that its expression is dependent on protein kinase A.

Impaired hippocampal plasticity in mice lacking the Cbeta1 catalytic subunit of cAMP-dependent protein kinase.

Neural pathways within the hippocampus undergo use-dependent changes in synaptic efficacy, and these changes are mediated by a number of signaling mechanisms, including cAMP-dependent protein kinase (PKA). The PKA holoenzyme is composed of regulatory and catalytic (C) subunits, both of which exist as multiple isoforms. There are two C subunit genes in mice, Calpha and Cbeta, and the Cbeta gene gives rise to several splice variants that are specifically expressed in discrete regions of the brain. We have used homologous recombination in embryonic stem cells to introduce an inactivating mutation into the mouse Cbeta gene, specifically targeting the Cbeta1-subunit isoform. Homozygous mutants showed normal viability and no obvious pathological defects, despite a complete lack of Cbeta1. The mice were analyzed in electrophysiological paradigms to test the role of this isoform in long-term modulation of synaptic transmission in the Schaffer collateral-CA1 pathway of the hippocampus. A high-frequency stimulus produced potentiation in both wild-type and Cbeta1-/- mice, but the mutants were unable to maintain the potentiated response, resulting in a late phase of long-term potentiation that was only 30% of controls. Paired pulse facilitation was unaffected in the mutant mice. Low-frequency stimulation produced long-term depression and depotentiation in wild-type mice but failed to produce lasting synaptic depression in the Cbeta1 -/- mutants. These data provide direct genetic evidence that PKA, and more specifically the Cbeta1 isoform, is required for long-term depression and depotentiation, as well as the late phase of long-term potentiation in the Schaffer collateral-CA1 pathway.

Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hippocampal CA1 pyramidal neurons: Ca(2+)-dependent activation by blocking A1 adenosine receptors.

When performed at increased external [Ca2+]/[Mg2+] ratio (2.5 mM/0.5 mM), temporary block of A1 adenosine receptors in hippocampus [by 8-cyclopentyltheophylline (CPT)] leads to a dramatic and irreversible change in the excitatory postsynaptic current (EPSC) evoked by Schaffer collateral/commissural (SCC) stimulation and recorded by in situ patch clamp in CA1 pyramidal neurons. The duration of the EPSC becomes stimulus dependent, increasing with increase in stimulus strength. The later occurring component of the EPSC is carried through N-methyl-D-aspartate (NMDA) receptor-operated channels but disappears under either the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These findings indicate that the late component of the SCC-evoked EPSC is polysynaptic: predominantly non-NMDA receptor-mediated SCC inputs excite CA1 neurons that recurrently excite each other by predominantly NDMA receptor-mediated synapses. These recurrent connections are normally silent but become active after CPT treatment, leading to enhancement of the late component of the EPSC. The activity of these connections is maintained for at least 2 hr after CPT removal. When all functional NMDA receptors are blocked by dizocilpine maleate (MK-801), subsequent application of CPT leads to a partial reappearance of NMDA receptor-mediated EPSCs evoked by SCC stimulation, indicating that latent NMDA receptors are recruited. Altogether, these findings indicate the existence of a powerful system of NMDA receptor-mediated synaptic contacts in SCC input to hippocampal CA1 pyramidal neurons and probably also in reciprocal connections between these neurons, which in the usual preparation are kept latent by activity of A1 receptors.

Cooperative interactions among afferents govern the induction of homosynaptic long-term depression in the hippocampus.

Prolonged periods of low-frequency stimulation have been shown to produce a robust, long-term synaptic depression (LTD) in both hippocampus and visual cortex. In the present study we have examined the extent to which interactions among afferents govern the induction of homosynaptic LTD in young-adult rats in hippocampal region CA1 in vitro. Field excitatory postsynaptic potentials were assessed before and after conditioning stimulation consisting of two 10-min trains of low-frequency stimulation (LFS; 1 Hz) of the Schaffer collateral/commissural pathway. LFS at an intensity producing a 0.5-mV response did not produce significant synaptic depression. However, LFS administered at a higher intensity resulted in significant input-specific LTD of a 0.5-mV test response. Picrotoxin, which also facilitates depolarization of CA1 neurons, significantly enhanced the magnitude of LTD after LFS at 0.5 mV. In addition, LFS at 0.5 mV in normal perfusion medium (no picrotoxin) produced only small changes in synaptic efficacy when either of two converging pathways was conditioned separately but produced a robust LTD when both pathways were conditioned simultaneously. This cooperative LTD was reversibly blocked by prior administration of 100 microM DL-aminophosphonovaleric acid but not by 20 microM nimodipine. Taken together, these results suggest that cooperative interactions among afferents contribute to voltage-dependent processes underlying the induction of homosynaptic LTD.

Layer-specific programs of development in neocortical projection neurons.

How are long-range axonal projections from the cerebral cortex orchestrated during development? By using both passively and actively transported axonal tracers in fetal and postnatal ferrets, we have analyzed the development of projections from the cortex to a number of thalamic nuclei. We report that the projections of a cortical area to its corresponding thalamic nuclei follow highly cell-specific programs of development. Axons from cells in the deepest layers of the cerebral cortex (layer 6 and superficial subplate neurons) appear to grow very slowly and be delayed for several weeks in the cerebral white matter, reaching the thalamus over a protracted period. Neurons of layer 5, on the other hand, develop their projections much faster; despite being born after the neurons of deeper layers, layer 5 neurons are the first to extend their axons out of the cortical hemisphere and innervate the thalamus. Layer 5 projections are massive in the first postnatal weeks but may become partly eliminated later in development, being overtaken in number by layer 6 cells that constitute the major corticothalamic projection by adulthood. Layer 5 projections are area-specific from the outset and arise as collateral branches of axons directed to the brainstem and spinal cord. Our findings show that the early development of corticofugal connections is determined not by the sequence of cortical neurogenesis but by developmental programs specific for each type of projection neuron. In addition, they demonstrate that in most thalamic nuclei, layer 5 neurons (and not subplate or layer 6 neurons) establish the first descending projections from the cerebral cortex.