Herramientas de gestión de compromiso para trabajadores del conocimiento

El objetivo de la línea de investigación seguida en esta tesis consiste en identificar palancas de gestión de las personas en las organizaciones que permitan mejorar su rendimiento mediante la gestión del compromiso de los profesionales de las organizaciones inmersas en la denominada sociedad del conocimiento. Para identificar dichas palancas se analizan algunos de los factores que, según la literatura científica, tienen como consecuencia cambios en la productividad, como son el compromiso organizacional y las conductas cívicas dentro de la organización. También, por su actualidad y relevancia en las prácticas de gestión de recursos humanos, se han analizado el impacto que tienen en estos factores en las prácticas empresariales que permiten conciliar vida profesional y personal el efecto del género en las distintas variables analizadas. Por todo lo anterior, en la investigación se analizan algunos de los factores de carácter psicosocial que promueven el compromiso en una organización, y se profundiza en dos conceptos: el análisis del compromiso de los profesionales con la organización para la que trabajan, y los comportamientos de ciudadanía organizativa que se exhiben en la organización por sus miembros. Para ello, se realiza un encuadramiento teórico de los siguientes conceptos: el compromiso como eje del trabajo; la ciudadanía organizativa como modelo cultural de la organización que promueve el compromiso; el rol de los líderes; los efectos de las políticas de conciliación; las diferencias de percepciones derivadas del género y un sistema de revisión de retributiva eficiente y coherente con el marco conceptual planteado. La metodología seleccionada para este trabajo ha sido el análisis en profundidad del caso de una empresa española, Red Eléctrica de España a través de tres pilares básicos: el primero consiste en el análisis exhaustivo de los datos obtenidos en las dos encuestas de clima social que dicha empresa realizó en el período 2006-2009; el segundo se centra en el desarrollo de un modelo matemático para el cálculo eficiente de recompensas salariales a través de un modelo de optimización; y el tercero es la consecuencia del conocimiento profundo que el autor tiene de la propia empresa, su cultura y funcionamiento, fruto de su experiencia profesional como directivo en el área de desarrollo de recursos humanos, función que desempeñó en la organización durante nueve años. En el análisis de este caso se ha investigado la influencia del género en el compromiso y la ciudadanía organizativa de los empleados de dicha organización, para identificar las diferencias de percepción que puedan ser explicadas por el género en una empresa muy masculina como es aquella. También, se ha incluido en este estudio de caso el análisis del efecto que presentan las medidas de conciliación en el compromiso de los empleados, por la relevancia que tiene este asunto en el panorama laboral español actual. Este análisis permite conocer hasta qué punto son o no motivadoras estas medidas en la organización analizada y, como consecuencia de ello, el tipo de gestión más oportuna de las mismas para conseguir no sólo los fines sociales que pretenden, garantizar que los empleados puedan compatibilizar sus exigencias laborales con una vida personal adecuada, sino también mejorar el clima, productividad y compromiso de éstos con la empresa. Para completar este análisis del caso, se han identificado de forma analítica los factores que mejor explican el clima de la organización y se ha concluido el papel central de la dirección que se concreta en la actuación de cada jefe, como motor del clima social en el equipo que dirige. Dado que la tesis pivota sobre el papel relevante que tiene la generación de una cultura de ciudadanía organizativa, se ha complementado el análisis con el desarrollo una herramienta de cálculo que facilita la determinación de los incrementos de la retribución fija de acuerdo con los principios de transparencia, equidad y justicia acordes con el modelo de empresa que promueve la virtud cívica de las personas empleadas en ella. Para ello se ha desarrollado un nuevo método de cálculo del incremento de retribución fija mediante un modelo analítico innovador y compacto de programación lineal entera mixta. Este modelo permite a las organizaciones realizar diseños de política retributiva de forma sencilla y rápida, a la vez que facilita la transparencia de las mismas en el proceso de gestión de la compensación. No se ha abordado el asunto de la determinación de la retribución variable, por ser un asunto relativamente menos complejo y profusamente tratado en la práctica directiva de las empresas. La primera de las conclusiones de la investigación realizada se refiere a los aspectos de la cultura organizativa que pueden identificarse como motores del compromiso. Se concluye que en el caso de estudio hay una fuerte relación mutua entre los rasgos que definen el compromiso emocional y los rasgos que determinan un comportamiento caracterizado como de ciudadanía organizativa. Se ha encontrado una correlación significativa y alta entre indicadores de compromiso y factores que recogen comportamientos de ciudadanía organizativa, correlación muy notable tanto para los factores de compromiso racional como para los de compromiso emocional. También se ha evidenciado que la correlación entre compromiso emocional y rasgos de comportamientos de ciudadanía organizacional es mayor que la que aparece entre compromiso racional y rasgos de comportamientos de ciudadanía organizacional. Desde el punto de vista de la práctica de gestión de recursos humanos, estas relaciones indican la conveniencia de promover una cultura organizacional basada en los principios de la ciudadanía organizativa para alcanzar altos niveles de compromiso emocional de los profesionales y mejorar la eficiencia organizativa. La segunda de las conclusiones se refiere al efecto de las políticas de conciliación en las organizaciones. Sobre este asunto se concluye que en el caso de estudio no puede considerarse que las medidas de conciliación tengan una fuerte relación con el compromiso emocional, y menos que puedan considerarse directamente una herramienta de generación de compromiso emocional. Sin embargo, sí que se detecta una cierta relación entre las percepciones de conciliación y de compromiso con la organización, y sobre todo, con el compromiso racional con la organización, que puede tener que ver con que para los empleados de la organización analizada, las medidas de conciliación son consideradas como una parte más de las condiciones laborales que ofrece la organización a los trabajadores. La tercera conclusión se refiere a la relación entre el género de los trabajadores y su nivel de compromiso y de ciudadanía organizativa. En el caso de estudio no se identifica una relación entre el género y el nivel de compromiso de los profesionales ni tampoco con la percepción de ciudadanía organizativa, variando la situación del período 2006 al período 2009. La cuarta conclusión se refiere al impacto que la actuación de los líderes (jefes) tiene en el clima social. En el caso de estudio, la actuación de los directivos y el nivel de compromiso que genera en los profesionales explica por sí sola más de un tercio de la varianza del clima organizativo, entendido como tal el que refleja el conjunto global de preguntas que constituyen la encuesta de clima del caso de estudio. Del análisis realizado se concluye que en el caso de estudio la percepción que los empleados tienen de sus jefes tiene un efecto relevante sobre el resto de percepciones de compromiso, ciudadanía organizativa y otros factores que conforman el clima social de la organización. La quinta y última conclusión supone la aportación de un modelo novedoso de cálculo de la recompensa económica coherente con un modelo de gestión empresarial mediante una cultura de ciudadanía organizativa. La solución que obtiene este modelo es el incremento salarial individual de cada profesional, que tiene en cuenta su rendimiento, posicionamiento salarial y encuadramiento profesional. Además de las restricciones presupuestarias, se consideran los principios de transparencia, equidad y justicia coherentes con el modelo conceptual planteado. La principal contribución de este trabajo es la formulación matemática de los criterios cualitativos que se emplean habitualmente en el proceso de revisión salarial. El método planteado supone una innovación que permite automatizar la metodología tradicional de gestión de incrementos salariales basados en matrices de incremento, así como evitar la aplicación de limitaciones en las valoraciones de desempeño derivadas de las restricciones presupuestarias que toda organización tiene. De esta manera se puede disponer de un mecanismo de revisión salarial que tiene en cuenta el desempeño de los profesionales, pero que permite la gestión “desacoplada” de la evaluación de rendimiento y la actualización de la retribución fija. ABSTRACT The aim of the research pursued in this thesis is to identify some human resources management levers in organizations to improve their performance through individual’s commitment management, focusing in organizations immersed in the so-called knowledge society. In order to find out these levers, the author analysed some of the psychosocial factors that promote engagement to the organizations and, according to the scientific literature, have effects in their productivity. These factors analysed are organisational commitment and citizenship behaviours. Additionally, the investigation also focuses on work-life balance policies and gender considerations, because of their relevance and topicality for the human resources’ policies. In the light of this, the investigation focuses on some of the psychosocial factors that promote organisational commitment, and delves into two concepts: the analysis of the commitment of professionals to the organization for which they work, and the organizational citizenship behaviours exhibited in the organization by its members. For this, a theoretical framework is performed for the following items: the professional’s commitment which is the pillar of this work; the organisational citizenship as a cultural model to promote that commitment; the role of the leaders; the effects of the work-life balance policies; the different perceptions of the professionals because of their gender; and an efficient salary review system, which is coherent with the conceptual framework set. The methodology selected for this work was the analysis in depth of the case of a Spanish company, Red Eléctrica de España, through three basic subjects: the first consists of a thorough analysis of the data obtained in the two work climate surveys made by this company in 2006 and 2009; the second focuses on the development of a mathematical model for calculating efficient salary reviews through an optimization model; and the third is the result of the author’s deep understanding of the company, its culture and its performance because of his professional experience as a manager in the area of human resource development, which was his role in the organization for nine years. The author investigated in the analysis of this case about the influence of gender on the employees’ organizational commitment and citizenship behaviours, in order to find out perception differences that can be explained by the highly masculine organisational culture such Red Eléctrica de España had during the studied period. Additionally, because of the importance of the work-life balance promotion in the Spanish labour scene, the case study analysis includes their effect in the employees’ commitment. This analysis allows to know motivating are these measures in the studied organization and, as a result, the most appropriate type of management thereof for social purposes, not only intended to ensure that employees can balance their work and personal demands, but also improving the work climate, the productivity and the organisational commitment. The investigation identifies the factors which best explain the work climate of the organization and concludes the central role of the leadership, embodied in the performance of every manager, to boost the work climate in their teams. Since this thesis pivots on the important role the generation of a culture of organizational citizenship has, the investigation has been complemented with the development of a analytic tool that facilitates the calculation of the salary review increments according to the principles of transparency, equity and justice in line with a work culture that promotes organisational citizenship behaviours. For this, this works develops a new method for calculating fixed salary increases through an innovative and compact mixed integer linear programming model. This model enables organizations to design compensation policies easily and quickly, and facilitates the transparency of the compensation management system. The method for determining variable remuneration has not been addressed because it is relatively less complex issue and widely discussed. The first conclusion of the conducted investigation concerns aspects of organizational culture that could be identified as commitment drivers. In the case study exists a strong and mutual relationship between the characteristics defining the emotional commitment and the organisational citizenship behaviours. The investigation has found out a meaningful and high correlation between indicators of commitment and the factors collecting organizational citizenship behaviour. This correlation with organisational citizenship is remarkable for both, rational and emotional, commitment. The correlation between organizational citizenship behaviours and emotional commitment and is greater than the one with rational commitment. From the practitioner point of view, these relationships show the importance of promoting an organizational culture based on the principles of organizational citizenship to achieve high levels of emotional engagement of professionals and improve organizational efficiency. The second conclusion relates to the effect of work-life balance policies in organizations. On this matter, the investigation concludes that for the case study, work-life balance measures do not have a strong relationship with the emotional commitment, and unless they can be usually considered as a tool to improve employees’ emotional commitment. However, a certain relationship between perceptions of work-life facilities and organisational commitment exists, especially with the rational commitment to the organization. This relationship appears because for employees of the analysed organization, work-life balance measures could be considered as a part of working conditions offered to them by the organization. The third conclusion concerns the relationship between the gender of workers and their level of commitment and organizational citizenship. In this case study, there is not any relationship between gender and the professional’s commitment level nor the perception of organizational citizenship; and the situation varies during the period studied. The fourth conclusion refers to the impact that the actions of the leaders have on the work climate. In the case study, the performance of management and the level of commitment generated, explains more than a third of the variance of work climate - understood as such reflecting the overall set of questions that constitute the work climate survey -. The analysis concludes that in the case study perception that employees have of their leaders has a significant effect on the rest of perceptions of commitment, organizational citizenship and other factors making the work climate of the organization. The fifth and last conclusion represents the contribution of a new model for calculating the salary increment, coherent with a corporate citizenship management culture. The solution obtained from this model consists of salary increases for each employee; these increases consider the employee’s professional performance, salary level relative to peers within the organization, and professional group. In addition to budget constraints, we modelled other elements typical of compensation systems, such as equity and justice. The major contribution of this work is the mathematical formulation of the criteria that are typically the basis for salary management. The compact formulation and the ease of obtaining the optimal solution facilitate its use in large companies that maintain very high levels of homogeneity across employees. Designing different strategies for specific groups within a company is also possible. A major benefit of this method is that it allows a company to independently manage its salary and assessment policies. Because obtaining salary-revision matrices without using the mathematical model we present in this paper is typically done iteratively by tuning previously defined matrices, managers commonly tune values for assessing employee performance to ensure that salary increases and performance assessments are consistent; however, this distorts the evaluation process and decreases employee motivation. In this MILP model, employee performance is only one parameter of several input parameters used in designing a salary policy that is independent of the results of performance-assessment values.

Compensation of biased excitation effects for MLS-based nonlinear systems' identification

MLS-based identification of nonlinear systems is largely affected by deviations in the excitation signal amenable to the combined effect of DC-offset and an arbitrary gain. These induce orthogonality loss in the MLS filter bank output, thus invalidating the underlying identification construction. In this paper we present a correction algorithm to derive the corrected Volterra kernels from the biased estimations provided by the standard MLS-based procedure.

On the actions that one nerve cell can have on another: Distinguishing “drivers” from “modulators”

When one nerve cell acts on another, its postsynaptic effect can vary greatly. In sensory systems, inputs from “drivers” can be differentiated from those of “modulators.” The driver can be identified as the transmitter of receptive field properties; the modulator can be identified as altering the probability of certain aspects of that transmission. Where receptive fields are not available, the distinction is more difficult and currently is undefined. We use the visual pathways, particularly the thalamic geniculate relay for which much relevant evidence is available, to explore ways in which drivers can be distinguished from modulators. The extent to which the distinction may apply first to other parts of the thalamus and then, possibly, to other parts of the brain is considered. We suggest the following distinctions: Cross-correlograms from driver inputs have sharper peaks than those from modulators; there are likely to be few drivers but many modulators for any one cell; and drivers are likely to act only through ionotropic receptors having a fast postsynaptic effect whereas modulators also are likely to activate metabotropic receptors having a slow and prolonged postsynaptic effect.

A Modified Positive Velocity and Position Feedback scheme with delay compensation for improved nanopositioning performance

Acknowledgments This paper was sponsored by the Spanish FPU12/00984 Program (Ministerio de Educacion, Cultura y Deporte). It was also sponsored by the Spanish Government Research Program with the Project DPI2012-37062-CO2-01 (Ministerio de Economia y Competitividad) and by the European Social Fund.

Distinct Actions and Cooperative Roles of ROCK and mDia in Rho Small G Protein-induced Reorganization of the Actin Cytoskeleton in Madin–Darby Canine Kidney Cells

Rho, a member of the Rho small G protein family, regulates the formation of stress fibers and focal adhesions in various types of cultured cells. We investigated here the actions of ROCK and mDia, both of which have been identified to be putative downstream target molecules of Rho, in Madin–Darby canine kidney cells. The dominant active mutant of RhoA induced the formation of parallel stress fibers and focal adhesions, whereas the dominant active mutant of ROCK induced the formation of stellate stress fibers and focal adhesions, and the dominant active mutant of mDia induced the weak formation of parallel stress fibers without affecting the formation of focal adhesions. In the presence of C3 ADP-ribosyltransferase for Rho, the dominant active mutant of ROCK induced the formation of stellate stress fibers and focal adhesions, whereas the dominant active mutant of mDia induced only the diffuse localization of actin filaments. These results indicate that ROCK and mDia show distinct actions in reorganization of the actin cytoskeleton. The dominant negative mutant of either ROCK or mDia inhibited the formation of stress fibers and focal adhesions, indicating that both ROCK and mDia are necessary for the formation of stress fibers and focal adhesions. Moreover, inactivation and reactivation of both ROCK and mDia were necessary for the 12-O-tetradecanoylphorbol-13-acetate–induced disassembly and reassembly, respectively, of stress fibers and focal adhesions. The morphologies of stress fibers and focal adhesions in the cells expressing both the dominant active mutants of ROCK and mDia were not identical to those induced by the dominant active mutant of Rho. These results indicate that at least ROCK and mDia cooperatively act as downstream target molecules of Rho in the Rho-induced reorganization of the actin cytoskeleton.

Sequential Actions of Phospholipase D and Phosphatidic Acid Phosphohydrolase 2b Generate Diglyceride in Mammalian Cells

Phosphatidylcholine (PC) is a major source of lipid-derived second messenger molecules that function as both intracellular and extracellular signals. PC-specific phospholipase D (PLD) and phosphatidic acid phosphohydrolase (PAP) are two pivotal enzymes in this signaling system, and they act in series to generate the biologically active lipids phosphatidic acid (PA) and diglyceride. The identity of the PAP enzyme involved in PLD-mediated signal transduction is unclear. We provide the first evidence for a functional role of a type 2 PAP, PAP2b, in the metabolism of PLD-generated PA. Our data indicate that PAP2b localizes to regions of the cell in which PC hydrolysis by PLD is taking place. Using a newly developed PAP2b-specific antibody, we have characterized the expression, posttranslational modification, and localization of endogenous PAP2b. Glycosylation and localization of PAP2b appear to be cell type and tissue specific. Biochemical fractionation and immunoprecipitation analyses revealed that PAP2b and PLD2 activities are present in caveolin-1–enriched detergent-resistant membrane microdomains. We found that PLD2 and PAP2b act sequentially to generate diglyceride within this specialized membrane compartment. The unique lipid composition of these membranes may provide a selective environment for the regulation and actions of enzymes involved in signaling through PC hydrolysis.

Cortical cell death induced by IL-1 is mediated via actions in the hypothalamus of the rat

The cytokine IL-1 mediates diverse forms of neurodegeneration, but its mechanism of action is unknown. We have demonstrated previously that exogenous and endogenous IL-1 acts specifically in the rat striatum to dramatically enhance ischemic and excitotoxic brain damage and cause extensive cortical injury. Here we tested the hypothesis that this distant effect of IL-1 is mediated through polysynaptic striatal outputs to the cortex via the hypothalamus. We show that IL-1β injected into the rat striatum with the excitotoxin α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA) caused increased expression of IL-1β (mRNA and protein) mainly in the cortex where maximum injury occurs. Marked increases in IL-1β mRNA and protein were also observed in the hypothalamus. S-AMPA, injected alone into the striatum, caused only localized damage, but administration of IL-1β into either the striatum or the lateral hypothalamus immediately after striatal S-AMPA resulted in widespread cell loss throughout the ipsilateral cortex. Finally we showed that the cortical cell death produced by striatal coinjection of S-AMPA and IL-1β was significantly reduced by administration of the IL-1 receptor antagonist into the lateral hypothalamus. These data suggest that IL-1β can act in the hypothalamus to modify cell viability in the cortex. We conclude that IL-1-dependent pathways project from the striatum to the cortex via the hypothalamus and lead to cortical injury, and that these may contribute to a number of human neurological conditions including stroke and head trauma.

The tomato ethylene receptors NR and LeETR4 are negative regulators of ethylene response and exhibit functional compensation within a multigene family

The plant hormone ethylene is involved in many developmental processes, including fruit ripening, abscission, senescence, and leaf epinasty. Tomato contains a family of ethylene receptors, designated LeETR1, LeETR2, NR, LeETR4, and LeETR5, with homology to the Arabidopsis ETR1 ethylene receptor. Transgenic plants with reduced LeETR4 gene expression display multiple symptoms of extreme ethylene sensitivity, including severe epinasty, enhanced flower senescence, and accelerated fruit ripening. Therefore, LeETR4 is a negative regulator of ethylene responses. Reduced expression of this single gene affects multiple developmental processes in tomato, whereas in Arabidopsis multiple ethylene receptors must be inactivated to increase ethylene response. Transgenic lines with reduced NR mRNA levels exhibit normal ethylene sensitivity but elevated levels of LeETR4 mRNA, indicating a functional compensation of LeETR4 for reduced NR expression. Overexpression of NR in lines with lowered LeETR4 gene expression eliminates the ethylene-sensitive phenotype, indicating that despite marked differences in structure these ethylene receptors are functionally redundant.

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0–12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12–24 hr, P implant removed; 24–36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3α-hydroxy-5α-pregnan-20-one, which operates through the type A γ-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.

Opposing mitogenic and anti-mitogenic actions of parathyroid hormone-related protein in vascular smooth muscle cells: A critical role for nuclear targeting

Parathyroid hormone-related protein (PTHrP) is a prohormone that is posttranslationally processed to a family of mature secretory forms, each of which has its own cognate receptor(s) on the cell surface that mediate the actions of PTHrP. In addition to being secreted via the classical secretory pathway and interacting with cell surface receptors in a paracrine/autocrine fashion, PTHrP appears to be able to enter the nucleus directly following translation and influence cellular events in an “intracrine” fashion. In this report, we demonstrate that PTHrP can be targeted to the nucleus in vascular smooth muscle cells, that this nuclear targeting is associated with a striking increase in mitogenesis, that this nuclear effect on proliferation is the diametric opposite of the effects of PTHrP resulting from interaction with cell surface receptors on vascular smooth muscle cells, and that the regions of the PTHrP sequence responsible for this nuclear targeting represent a classical bipartite nuclear localization signal. This report describes the activation of the cell cycle in association with nuclear localization of PTHrP in any cell type. These findings have important implications for the normal physiology of PTHrP in the many tissues which produce it, and suggest that gene delivery of PTHrP or modified variants may be useful in the management of atherosclerotic vascular disease.

Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation

Normal aging is associated with a significant reduction in cognitive function across primate species. However, the structural and molecular basis for this age-related decline in neural function has yet to be defined clearly. Extensive cell loss does not occur as a consequence of normal aging in human and nonhuman primate species. More recent studies have demonstrated significant reductions in functional neuronal markers in subcortical brain regions in primates as a consequence of aging, including dopaminergic and cholinergic systems, although corresponding losses in cortical innervation from these neurons have not been investigated. In the present study, we report that aging is associated with a significant 25% reduction in cortical innervation by cholinergic systems in rhesus monkeys (P < 0.001). Further, these age-related reductions are ameliorated by cellular delivery of human nerve growth factor to cholinergic somata in the basal forebrain, restoring levels of cholinergic innervation in the cortex to those of young monkeys (P = 0.89). Thus, (i) aging is associated with a significant reduction in cortical cholinergic innervation; (ii) this reduction is reversible by growth-factor delivery; and (iii) growth factors can remodel axonal terminal fields at a distance, representing a nontropic action of growth factors in modulating adult neuronal structure and function (i.e., administration of growth factors to cholinergic somata significantly increases axon density in terminal fields). These findings are relevant to potential clinical uses of growth factors to treat neurological disorders.

Intervening in evolution: Ethics and actions

Biologists should help to guide a process of cultural evolution in which society determines how much effort, if any, is ethically required to preserve options in biological evolution. Evolutionists, conservation biologists, and ecologists should be doing more research to determine actions that would best help to avoid foreclosing evolutionary options.

Study to assess the compensation and skills of medical library professionals relative to information technology professionals*

Purpose: The study seeks to determine how medical library professionals performing information-technology (IT) roles are compensated and how their positions are designed compared to information technology staff in their institutions.

Opposite actions of nitric oxide on cholinergic synapses: which pathways?

Nitric oxide (NO) produced opposite effects on acetylcholine (ACh) release in identified neuroneuronal Aplysia synapses depending on the excitatory or the inhibitory nature of the synapse. Extracellular application of the NO donor, SIN-1, depressed the inhibitory postsynaptic currents (IPSCs) and enhanced the excitatory postsynaptic currents (EPSCs) evoked by presynaptic action potentials (1/60 Hz). Application of a membrane-permeant cGMP analog mimicked the effect of SIN-1 suggesting the participation of guanylate cyclase in the NO pathway. The guanylate cyclase inhibitor, methylene blue, blocked the NO-induced enhancement of EPSCs but only reduced the inhibition of IPSCs indicating that an additional mechanism participates to the depression of synaptic transmission by NO. Using nicotinamide, an inhibitor of ADP-ribosylation, we found that the NO-induced depression of ACh release on the inhibitory synapse also involves ADP-ribosylation mechanism(s). Furthermore, application of SIN-1 paired with cGMP-dependent protein kinase (cGMP-PK) inhibitors showed that cGMP-PK could play a role in the potentiating but not in the depressing effect of NO on ACh release. Increasing the frequency of stimulation of the presynaptic neuron from 1/60 Hz to 0.25 or 1 Hz potentiated the EPSCs and reduced the IPSCs. In these conditions, the potentiating effect of NO on the excitatory synapse was reduced, whereas its depressing effect on the inhibitory synapse was unaffected. Moreover the frequency-dependent enhancement of ACh release in the excitatory synapse was greatly reduced by the inhibition of NO synthase. Our results indicate that NO may be involved in different ways of modulation of synaptic transmission depending on the type of the synapse including synaptic plasticity.