Fragile X syndrome (FXS) causes mental impairment and autism through transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein fragile X mental retardation protein (FMRP). Cortical pyramidal neurons in affected individuals and Fmr1 knock-out (KO) mice have an increased density of dendritic spines. The mutant mice also show defects in synaptic and experiencedependent circuit plasticity, which are known to be mediated in part by dendritic spine dynamics. We used in vivo time-lapse imaging with two-photon microscopy through cranial windows in male and female neonatal mice to test the hypothesis that dynamics of dendritic protrusions are altered in KO mice during early postnatal development. We find that layer 2/3 neurons from wild-type mice exhibit a rapid decrease in dendritic spine dynamics during the first 2 postnatal weeks, as immature filopodia are replaced by mushroom spines. In contrast, KO mice show a developmental delay in the downregulation of spine turnover and in the transition from immature to mature spine subtypes. Blockade of metabotropic glutamate receptor (mGluR) signaling, which reverses some adult phenotypes of KO mice, accentuated this immature protrusion phenotype in KO mice. Thus, absence of FMRP delays spine stabilization and dysregulated mGluR signaling in FXS may partially normalize this early synaptic defect.

Fragile X syndrome (FXS), the most common inherited from of autism and mental impairment, is caused by transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein FMRP. Dendritic spines of cortical pyramidal neurons in affected individuals are abnormally immature and in Fmr1 knockout (KO) mice they are also abnormally unstable. This could result in defects in synaptogenesis, because spine dynamics are critical for synapse formation. We have previously shown that the earliest dendritic protrusions, which are highly dynamic and might serve an exploratory role to reach out for axons, elongate in response to glutamate. Here, we tested the hypothesis that this process is mediated by metabotropic glutamate receptors (mGluRs) and that it is defective in Fmr1 KO mice. Using time-lapse imaging with two-photon microscopy in acute brain slices from early postnatal mice, we find that early dendritic protrusions in layer 2/3 neurons become longer in response to application of glutamate or DHPG, a Group 1 mGluR agonist. Blockade of mGluR5 signaling, which reverses some adult phenotypes of KO mice, prevented the glutamate-mediated elongation of early protrusions. In contrast, dendritic protrusions from KO mice failed to respond to glutamate. Thus, absence of FMRP may impair the ability of cortical pyramidal neurons to respond to glutamate released from nearby pre-synaptic terminals, which may be a critical step to initiate synaptogenesis and stabilize spines.

ResumenEl material particulado (PM10), es un contaminante atmosférico capaz de ocasionar una grave problemática en cuanto a calidad del aire y afecciones en la salud humana. Por lo que en la presente investigación se presenta el análisis de las concentraciones de material particulado (PM10) en el sector del aeropuerto de Tababela en el Distrito Metropolitano de Quito, cuyo objetivo es determinar el método más apropiado para la medición de concentración de material particulado (PM10), mediante análisis geoestadístico de tres métodos: IDW, Spline y Kriging por medio del Software ArcGIS, con la finalidad de identificar los puntos de mayor concentración de PM10 en la zona de estudio. La toma de datos se realizó utilizando un muestreador casero, al igual que los datos obtenidos de la Red Metropolitana de Monitoreo Atmosférico de Quito (REMMAQ) ubicada en el sector de Carapungo; con estos se valida la metodología de muestreo mediante el método de regresión lineal o mínimos cuadrados, se muestra la utilidad del muestreador casero. Se recolectó los datos de concentración en 16 puntos estratégicos con duplicados cada uno que cubren la ruta Collas, con los que se obtuvo mapas de la zona analizada uno por cada método propuesto, los mismos se validaron mediante la aplicación de la herramienta Arctoolbox relacionando los datos obtenidos con respecto al blanco, se presenta que el valor de incertidumbre indica una proximidad en relación a la concentración real; siendo el modelo Inverse distance weighted (IDW) el que respondió de mejor manera al comportamiento de PM10 en la zona permitiendo así obtener el mejor modelo que diferencie los puntos de menor y mayor concentración de PM10, a diferencia de los modelos Spline y Kriging.