43 research outputs found

    Stimulation of VTA dopamine inputs to LH upregulates orexin neuronal activity in a DRD2-dependent manner

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    Dopamine and orexins (hypocretins) play important roles in regulating reward-seeking behaviors. It is known that hypothalamic orexinergic neurons project to dopamine neurons in the ventral tegmental area (VTA), where they can stimulate dopaminergic neuronal activity. Although there are reciprocal connections between dopaminergic and orexinergic systems, whether and how dopamine regulates the activity of orexin neurons is currently not known. Here we implemented an opto-Pavlovian task in which mice learn to associate a sensory cue with optogenetic dopamine neuron stimulation to investigate the relationship between dopamine release and orexin neuron activity in the LH. We found that dopamine release can be evoked in LH upon optogenetic stimulation of VTA dopamine neurons, and is also naturally evoked by cue presentation after opto-Pavlovian learning. Furthermore, orexin neuron activity could also be upregulated by local stimulation of dopaminergic terminals in the LH in a way that is partially dependent on dopamine D2 receptors (DRD2). Our results reveal previously unknown orexinergic coding of reward expectation and unveil an orexin-regulatory axis mediated by local dopamine inputs in the LH. Optical VTA DA neuron stimulation is sufficient to elicit a Pavlovian-like dopamine transient in the NAc Dopamine in the LH encodes both negative and positive reward prediction errors Dopamine in the LH positively modulates orexin neuronal activity locally in a D2R dependent wa

    The epidermal growth factor receptor (EGRF) in lung cancer

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    Altres ajuts: Work in Dr Rosell's laboratory is partially supported by a grant from Fundació La CaixaIn the last decade, important advances have been made in understanding of cancer biology, particularly non-small-cell lung cancer (NSCLC) with the discovery of oncogenic drivers of the disease. The epidermal growth factor receptor (EGFR) gene and its pathways was the first oncogenic driver discovered to be mutated and treatable in lung cancer. Treatment with EGFR tyrosine kinase inhibitors (TKIs) is the standard of care for molecularly selected EGFR -mutant patients, while its role in unselected lung cancer patients is nowadays controversial. This review will provide an overview of the EGFR pathway and options for its treatment of lung cancer

    La imagen de Europa en los espots electorales en España. Elecciones al Parlamento Europeo 1987-2004

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    Impacte de les mutacions del gen KRAS en pacients afectes de carcinoma no microcític de pulmó estadi IV i la seva relació amb altres biomarcadors

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    Hem analitzat la mutació KRAS i els seus subtipus en mostres tumorals de 114 pacients diagnosticats d'un carcinoma de pulmó estadi IV. Un 21,9% dels pacients presentaren la mutació de KRAS. Dels seus subtipus, la més freqüent va ser G12C (44%). Dels pacients tractats amb quimioteràpia s'obtingueren un 4,8% de respostes completes i un 47,6% presentaren progressió de la malaltia. S'observà una tendència significativa a menor temps fins a la progressió i major supervivència global acord amb el performance status i els nivells de RAP 80.Els pacients KRAS-G12C presentaren una tendència no significativa a major supervivència global respecte els altres

    Striatum-projecting prefrontal cortex neurons support working memory maintenance

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    Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that dorsomedial striatum (dmStr)-projecting mPFC neurons are essential for WM maintenance, but not encoding or retrieval, in a T-maze spatial memory task. Fiber photometry of GCaMP6m-labeled mPFC→dmStr neurons revealed strongest activity during the maintenance period, and optogenetic inhibition of these neurons impaired performance only when applied during this period. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the maintenance period—alleviated WM impairment induced by NMDA receptor blockade. Moreover, cellular-resolution miniscope imaging revealed that >50% of mPFC→dmStr neurons are active during WM maintenance and that this subpopulation is distinct from neurons active during encoding and retrieval. In all task periods, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance

    Study of the effect of EAFD in polymer composites usig DoE

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    This study assesses the processing behaviour and mechanical properties of different polymers widely used in several industry fields formulated with Electric Arc Furnace Dust (EAFD) as filler. Design of Experiments (DoE) has been proved to be an effective tool to obtain the maximum information with the minimum number of experiments. In this experimental design mechanical properties as well as the melt flow index were chosen as dependent variables. The effect of CaCO3, BaSO4 and EAFD fillers as well as different polymer matrix has been evaluated.Peer ReviewedPostprint (published version

    Alimentació : guia informativa i proposta d'activitats per promoure l'alimentació agroecològica

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    Forma part de la col·lecció: Col·lecció guies d'Escoles + Sostenibles;

    Screening for coping style increases the power of gene expression studies

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    Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data
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