Background: The study of the attentional system remains a challenge for current neuroscience. The “Attention Network Test” (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures.Results: This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1.Conclusions: The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects.

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ApoER2 is a member of the low density-lipoprotein receptor (LDL-R) family. As a receptor for reelin, ApoER2 participates in neuronal migration during development as well as synaptic plasticity and survival in the adult brain. A previous yeast two-hybrid screen showed that ApoER2 is a binding partner of sorting nexin 17 (SNX17) - a cytosolic adaptor protein that regulates the trafficking of several membrane proteins in the endosomal pathway, including LRP1, P-selectin and integrins. However, no further studies have been performed to investigate the role of SNX17 in ApoER2 trafficking and function. In this study, we present evidence based on GST pull-down and inmunoprecipitation assays that the cytoplasmic NPxY endocytosis motif of ApoER2 interacts with the FERM domain of SNX17. SNX17 stimulates ApoER2 recycling in different cell lines including neurons without affecting its endocytic rate and also facilitates the transport of ApoER2 from the early endosomes to the recycling endosomes. The reduction of SNX17 was associated with accumulation of an ApoER2 carboxy-terminal fragment (CTF). In addition, in SNX17 knockdown cells, constitutive ApoER2 degradation was not modified, whereas reelin-induced ApoER2 degradation was increased, implying that SNX17 is a regulator of the receptor's half-life. Finally, in SNX17 silenced hippocampal and cortical neurons, we underscored a positive role of this endosomal protein in the development of the dendritic tree and reelin signaling. Overall, these results establish the role of SNX17 in ApoER2 trafficking and function and aid in identifying new links between endocytic trafficking and receptor signaling.

Introducción. Existen diversas evidencias de que el proceso de envejecimiento natural ocasiona un declive en las diferentes funciones cognitivas, incluyendo la atención. Objetivo. Determinar cómo afecta el envejecimiento saludable a las diferentes redes atencionales. Sujetos y métodos. Dos grupos de estudio: jóvenes (32,5 ± 9,7 años) y adultos mayores saludables (62,7 ± 4,7 años). Como instrumento para evaluar la atención utilizamos el test de redes atencionales-Attention Network Test (ANT)-. Resultados. En el ANT, en lo que respecta al tiempo de reacción ante las diferentes condiciones que se dan (sin clave, clave central, clave espacial, congruencia e incongruencia), encontramos diferencias significativas en todas ellas entre ambos grupos (p < 0,001). En cuanto al análisis de redes, éstas no mostraron diferencias entre ambas muestras. Si comparamos el efecto por bloques del ANT, el análisis post hoc mostró que la red de orientación para los sujetos jóvenes presenta un beneficio por el uso de las claves espaciales en el primer bloque, mientras que para los sexagenarios no. Además, la red de alerta mostró un mayor efecto en el primer bloque respecto del segundo en los adultos mayores y el efecto opuesto para la red ejecutiva y de orientación. Conclusiones. Los datos obtenidos muestran que existe una disminución en la velocidad de procesamiento en las personas mayores. En el caso particular de la red de orientación parece que los mayores requieren un intervalo temporal mayor para emplear las claves espaciales, aunque posteriormente tras cierto entrenamiento pueden beneficiarse de éstas casi al mismo nivel que los sujetos jóvenes. Palabras clave. Attention Network Test. Envejecimiento saludable. Red neural de alerta. Red neural ejecutiva. Red neural de orientación. Tiempo de reacción.

BackgroundApoER2 and the neurotrophin receptors Trk and p75NTR are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75NTR are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75NTR mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors.ResultsWe found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75NTR. Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF).ConclusionsOur results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.