Mecanismos celulares que subyacen a la "spike timing-dependent plasticity"

Programa de Doctorado en NeurocienciasLa Spike timing-dependent plasticity (STDP) es una regla Hebbiana de aprendizaje involucrada en el refinamiento de las sinapsis durante el desarrollo y en procesos de aprendizaje y memoria en adultos. Dada su importancia en dichos procesos, es sorprendente lo poco que se conoce sobre el papel y las reglas que gobiernan la STDP en el hipocampo. En la presente tesis doctoral se investigaron los requerimientos mínimos para la inducción de la potenciación y la depresión de larga duración dependientes de la coincidencia temporal entre la actividad pre y postsináptica (t-LTP y t-LTD respectivamente, del inglés timing-dependent long-term potentiation y timing-dependent long-term depression), así como los mecanismos celulares que subyacen a estas dos formas de plasticidad en las sinapsis establecida entre las colaterales de Schaffer de las neuronas de CA3 y las células piramidales de CA1 (CA3-CA1) en el hipocampo de ratones juveniles (P12-P18). Para ello, se utilizó la técnica de patch clamp en su configuración de célula completa. Se encontró que tanto la t-LTP como la t-LTD pueden inducirse en dicha sinapsis mediante el pareamiento de la actividad presináptica con un único potencial de acción postsináptico a baja frecuencia de estimulación (0.2 Hz). Tanto la t-LTP como la t-LTD requieren receptores de glutamato de tipo NMDA para su inducción, pero la localización y las propiedades de dichos receptores son diferentes: la t-LTP requiere receptores de tipo NMDA postsinápticos, pero no la t-LTD; y mientras que la t-LTP requiere receptores de tipo NMDA que contienen la subunidades GluN2A y GluN2B, la t-LTD requiere receptores de tipo NMDA que contienen las subunidades GluN2C y/o GluN2D. Tanto la t-LTP como la t-LTD requieren entrada de calcio postsináptico para su inducción. La t-LTD requiere la entrada de calcio a través de canales de calcio dependientes de voltaje de tipo L, así como la liberación de calcio desde los reservorios intracelulares. Dicha liberación está mediada por la activación de receptores metabotrópicos de glutamato de tipo 5 (mGlu5). La inducción de la t-LTD requiere además la síntesis y liberación de endocannabinoides, así como la activación de receptores cannabinoides CB1. Tal como indican los análisis de las fluctuaciones de las respuestas, del número de fallos y del ratio por pares de pulsos, la t-LTD se expresa presinápticamente. Estos resultados muestran que la sinapsis CA3-CA1 exhibe tanto t-LTP como t-LTD dependientes de receptores de tipo NMDA durante el desarrollo y la identificación de una forma de LTD hipocampal presináptica involucrada en el refinamiento de las sinapsis.Universidad Pablo de Olavide. Departamento de Fisiología, Anatomía y Biología Celula

Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus.

Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12-P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca(2+) for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca(2+) release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a presynaptic form of hippocampal t-LTD similar to that previously described at neocortical synapses during development.Ministerio de Ciencia e Innovación/European Regional Development Fund (Grant ID: BFU2009-10034)This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/cercor/bhw17

El activismo en las migrantes trabajadoras del hogar: estudio cualitativo en el sur de España

El trabajo del hogar es un nicho ocupacional opresivo para las mujeres migrantes. Las estrategias que emplean para resistir esta situación han sido poco estudiadas. Este trabajo se interesa por su activismo. Mediante un estudio cualitativo en el sur de España se explora el sentido de dicha acción sociopolítica para las mujeres migrantes. En la primavera de 2020 se entrevistó a once activistas de la Asociación de Trabajadoras y Trabajadores del Hogar de Sevilla. El material se sometió a análisis de contenido. Los significados asociados a su activismo fueron agrupados en cuatro categorías: (1) el horizonte de lucha, (2) las formas de lucha, (3) los niveles de implicación y (4) los retos. Los resultados se limitan a un caso históricamente reciente, y a una muestra pequeña elegida propositivamente; sin embargo, aportan a la comprensión de la agencia de las migrantes, y abre campos de reflexión para las organizaciones de trabajadoras del hogar

A descriptive and quantitative approach regarding erosion and development of landforms on abandoned mine tailings: New insights and environmental implications from SE Spain

The San Cristóbal–Perules mining site in Mazarrón in southeast Spain was subjected to about a hundred years of intense mining activity for lead, silver, and zinc. Metallurgical operations (smelting, calcination, gravity concentration) carried out during the late nineteenth century–early twentieth century induced significant land transformation, and the most conspicuous wastes of this period consist of a chaotic piling of ‘old’ tailing deposits. Later on, during the mid-twentieth century, ‘modern’ tailings resulting from froth flotation were accumulated filling small valleys; these latter valley-fill tailings rose sequentially according to the upstream construction method, progressively raising the level of the dam during the process. Once abandoned, both types of tailing deposits underwent severe erosion, resulting in a mosaic of erosional and sedimentary landforms developed upon (e.g., gully formation) and within them (e.g., piping). We made an inventory and classification of these landforms. Our study shows the geomorphic work to reestablish a new steady state between the tailings deposits and the local erosive conditions. This scenario implies several hazards related to the extremely high heavy metal contents of these tailings and the geomorphic instability of the deposits. We also quantified the tailings tonnage and erosion that occurred at one of the tailings dams (El Roble). As shown by an oblique aerial photograph taken in 1968, this dam had a terraced topography, whereas in 2013 this morphology had evolved into a badland-type relief with deep parallel gullies. By recognizing and surveying specific, remnant points along the benches and outslopes of the older terraced topography, we were able to build up a first digital elevation model (DEM1) reflecting the initial topography. A second DEM, this time showing the present topography, allowed quantification of erosion via Material Loss = DEM1 − DEM2. This yields an erosion rate (1968–2009) of 151.8 Mg (MT) ha− 1 y− 1, which matches well typical values for erosion of mined areas, commonly above 100 Mg (MT) ha− 1 y− 1. Abandoned mine tailing deposits are extremely common in the semiarid scenarios of the SW USA, Australia, Chile, and Peru. Given the similarities of these scenarios with SE Spain, the example from Mazarrón may provide useful new insights regarding the erosion and geomorphic evolution of such tailing deposits. These matters should be addressed in key environmental actions such as mine closure plans and land reclamation projects. A solution may come via restoration of these deposits through landform design involving the building up of stable mature landscapes, which in turn can withstand erosion much more easily.Peer reviewe

Effects of human versus mouse leukemia inhibitory factor on the in vitro development of bovine embryos

Leukemia inhibitory factor (LIF) is a cytokine that shows conflicting effects on in vitro produced (IVP) bovine embryos. Bovine LIF (bLIF) has been cloned and used in culture, but there is no commercially available bLIF. Thus, researchers use human LIF (hLIF) to supplement the culture medium for bovine embryos because of its greater sequence homology compared to murine LIF (mLIF). We compared the effects of mLIF and hLIF on the development of bovine embryos in culture with the effects described for bLIF. Oocytes were matured and fertilized in vitro and cultured in modified synthetic oviduct fluid with BSA. On Day 6 post-insemination, morulae were cultured for 48 h in the presence of: (1) mLIF, 100 ng ml−1; (2) hLIF, 100 ng ml−1; or (3) no LIF. Reduced blastocyst rates were observed on Day 8 for hLIF at the middle and expanded stages, while mLIF had no effect. In contrast, Day 8 blastocysts showed decreased cell counts both in terms of inner cell mass (ICM) and ICM/total cell proportions in the presence of mLIF, while hLIF had no effect. No changes were seen in trophectoderm (TE) and total cell counts. The increased hatching rates and TE cell counts previously described for bLIF, together with the disparate effects exhibited by hLIF and mLIF during blastocyst formation indicate these compounds are inappropriate to replace bLIF. We recommend that heterospecific LIF should not be used to supplement the culture medium for bovine embryo or embryonic stem cells