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The ability to learn and form memories allows animals to adapt their behavior based on previous experiences. Associative learning, the process through which organisms learn about the relationship between two distinct events, has been extensively studied in various animal taxa. However, the existence of associative learning, prior to the emergence of centralized nervous systems in bilaterian animals, remains unclear. Cnidarians such as sea anemones or jellyfish possess a nerve net, which lacks centralization. As the sister group to bilaterians, they are particularly well suited for studying the evolution of nervous system functions. Here, we probe the capacity of the starlet sea anemone Nematostella vectensis to form associative memories by using a classical conditioning approach. We developed a protocol combining light as the conditioned stimulus with an electric shock as the aversive unconditioned stimulus. After repetitive training, animals exhibited a conditioned response to light alone indicating that they learned the association. In contrast, all control conditions did not form associative memories. Besides shedding light on an aspect of cnidarian behavior, these results root associative learning before the emergence of NS centralization in the metazoan lineage and raise fundamental questions about the origin and evolution of cognition in brainless animals.

L’estudi de l’activitat cardíaca en fetus és una eina vital per conèixer i monitorar la resposta del cor a diferents estímuls i, el comportament d’altres sistemes que l’afecten, com el sistema nerviós. Un dels paràmetres més emprats per estudiar el cor és la variabilitat del ritme cardíac (Heart Rate Variability, HRV). Existeixen diferents dispositius que permeten obtenir la freqüència cardíaca fetal, i conseqüentment, la HRV. En el present treball, s’ha fet ús d’un micròfon connectat a la sortida d’un cardiotocògraf per registrar els sons cardíacs d’un fetus. Aquest projecte té com a objectiu analitzar l’activitat cardíaca fetal per estudiar la influència de diferents estímuls auditius en forma de veu. S’han emprat diferents mètodes de processament de senyals per obtenir els paràmetres referents a la HRV, com per exemple filtrar, interpolar, calcular l’envolupant i la densitat espectral de potència. Els resultats obtinguts permeten analitzar el comportament cardíac d’un fetus influenciat per una veu externa. Els paràmetres temporals de la HRV augmenten a mesura que avança el registre, és a dir que la variabilitat del ritme cardíac creix. A la vegada, hi ha un canvi de predominança de la banda de freqüència. En un inici, la HF presenta una major potència, fet que es veu invertit cap al final del registre fonogràfic. Aquest fet s’assimila a què el fetus passa d’estar en repòs a estar actiu, però relaxat, i cap al final de la prova, sembla que es comença a estressar. Els resultats obtinguts s'han de contrastar en una base de dades major, que permeti determinar si aquests resultats són generalitzables, i analitzar si hi ha altres factors que puguin influenciar la resposta cardíaca del fetus. El estudio de la actividad cardíaca en fetos es una herramienta vital para conocer y monitorizar la respuesta del corazón a diferentes estímulos y, el comportamiento de otros sistemas que le afectan, como el sistema nervioso. Uno de los parámetros más empleados para estudiar el corazón es la variabilidad del ritmo cardíaco (Heart Rate Variability, HRV). Existen diferentes dispositivos que permiten obtener la frecuencia cardíaca fetal y, por tanto, la HRV. En el presente trabajo se ha utilizado un micrófono conectado a la salida de un cardiotocógrafo para registrar los sonidos cardíacos de un feto. Este proyecto tiene como objetivo analizar la actividad cardíaca fetal para estudiar la influencia de diferentes estímulos auditivos en forma de voz. Se han empleado diferentes métodos de procesamiento de señales para obtener los parámetros referentes a la HRV, como por ejemplo filtrar, interpolar, calcular el envolvente y la densidad espectral de potencia. Los resultados obtenidos permiten analizar el comportamiento cardíaco de un feto influenciado por una voz externa. Los parámetros temporales de la HRV aumentan a medida que avanza el registro, es decir, la variabilidad del ritmo cardíaco aumenta. A su vez, hay un cambio de predominancia de la banda de frecuencia. En un inicio, la HF presenta una mayor potencia, factor que se ve invertido en el final del registro fonográfico. Este hecho se asimila a que el feto pasa de estar en reposo a estar activo, pero relajado, y al final de la prueba, parece que se empieza a estresar. Los resultados obtenidos se deben contrastar en una base de datos mayor, que permita determinar si estos resultados son generalizables, y analizar si hay otros factores que puedan influir en la respuesta cardíaca del feto. The study of cardiac activity in fetuses is a vital tool for understanding and monitoring the response of the heart to different stimuli and the behavior of other systems that affect it, such as the nervous system. One of the most commonly used parameters to study the heart is the Heart Rate Variability (HRV). There are different devices that allow obtaining the fetal heart rate, and consequently, the HRV. In the present work, a microphone connected to the output of a cardiotocograph has been used to record the heart sounds of a fetus. The aim of this project is to analyze fetal cardiac activity in order to study the influence of different auditory stimuli in the form of a voice. Different signal processing methods have been used to obtain the HRV parameters, such as filtering, interpolation, calculation of the envelope and power spectral density. The results obtained allow us to analyze the cardiac behavior of a fetus influenced by an external voice. The time parameters of the HRV increase as the recording progresses, i.e., the variability of the heart rate increases. At the same time, there is a change in the predominance of the frequency band. Initially, HF presents a greater power, a fact that is reversed towards the end of the phonographic recording. This is likened to the fetus going from being at rest to being active, but relaxed, and at the end of the test, it appears to start to become stressed. The results obtained should be checked against a large database to determine whether these results are generalizable, and to analyze whether there are other factors that may influence the fetal cardiac response.

BackgroundDisruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset.MethodsTwenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls.ResultsRelative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence.ConclusionOur findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.

The International University of Andalucía (UNIA) Current Trends in Biomedicine Workshop on Molecular Causes of Primary Microcephaly and Related Diseases took place in Baeza, Spain, November 18–20, 2019. This meeting brought together scientists from Europe, the USA and China to discuss recent advances in our molecular and genetic understanding of a group of rare neurodevelopmental diseases characterised by primary microcephaly, a condition in which head circumference is smaller than normal at birth. Microcephaly can be caused by inherited mutations that affect key cellular processes, or environmental exposure to radiation or other toxins. It can also result from viral infection, as exemplified by the recent Zika virus outbreak in South America. Here we summarise a number of the scientific advances presented and topics discussed at the meeting.

Data de publicació electrònica: 31-12-2019 Background: Vagus nerve stimulation (VNS) using non-invasive approaches have attracted great attention due to their anti-epileptic, anti-depressive and pro-cognitive effects. It has been proposed that auricular transcutaneous VNS (atVNS) could benefit intellectual disability disorders, but preclinical data supporting this idea is limited. Objective: To develop an atVNS device for mice and to test its efficacy on memory performance in naïve mice and in a mouse model for intellectual disability. Methods: Naïve outbreed CD-1 mice and a model for fragile X syndrome, the Fmr1 knockout (Fmr1KO), were used to assess the effect of atVNS in the novel object-recognition memory performance. Results: We found that atVNS significantly improves memory persistence in naïve mice. Notably, atVNS was efficacious in normalizing the object-recognition memory deficit in the Fmr1KO model. Conclusion: Our data show that atVNS improves memory persistence in naïve mice and in a model of intellectual disability and support further studies taking advantage of preclinical mouse models of cognitive disorders. This work was supported by a Predoctoral fellowship from Jerome Lejeune Foundation (Spanish division) (A.V.-O.) and from “la Caixa” Foundation (ID 100010434), LCF/BQ/IN18/11660012 and European Union’s Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713673 (C.B.-P.). Ministerio de Economía, Innovación y Competitividad (MINECO) [#RTI2018-099282-B-I00 to A.O., #SAF2017-84060-R to R.M.]; the Instituto de Salud Carlos III [#RD16/0017/0020 to R.M.]; the Generalitat de Catalunya [2017SGR-669 to R.M.]; the ICREA (Institució Catalana de Recerca i Estudis Avançats) Acadèmia to A.O., A.I. and R.M.; Grant “Unidad de Excelencia María de Maeztu”, funded by the MINECO [#MDM-2014-0370]; PLAN E (Plan Español para el Estímulo de la Economía y el Empleo). FEDER (Fondo Europeo de Desarrollo Regional) funding is also acknowledged

Forkhead box (Fox) genes belong to the “winged helix” transcription factor superfamily. The function of some Fox genes is well known, such as the role of foxO in controlling metabolism and longevity and foxA in controlling differentiation of endodermal tissues. However, the role of some Fox factors is not yet well characterized. Such is the case of FoxK genes, which are mainly studied in mammals and have been implicated in diverse processes including cell proliferation, tissue differentiation and carcinogenesis. Planarians are free-living flatworms, whose importance in biomedical research lies in their regeneration capacity. Planarians possess a wide population of pluripotent adult stem cells, called neoblasts, which allow them to regenerate any body part after injury. In a recent study, we identified three foxK paralogs in the genome of Schmidtea mediterranea. In this study, we demonstrate that foxK1 inhibition prevents regeneration of the ectodermal tissues, including the nervous system and the epidermis. These results correlate with foxK1 expression in neoblasts and in neural progenitors. Although the triggering of wound genes expression, polarity reestablishment and proliferation was not affected after foxK1 silencing, the apoptotic response was decreased. Altogether, these results suggest that foxK1 would be required for differentiation and maintenance of ectodermal tissues.

Les malalties inflamatòries poden afectar qualsevol òrgan del cos. En aquests trastorns intervé el sistema immunitari, que genera una resposta inespecífica l'objectiu de la qual és aïllar possibles agents infecciosos. Tot i que es coneixen molt bé els mecanismes fisiològics dels processos inflamatoris, sovint la causa original de la inflamació és desconeguda, especialment en els casos d'inflamacions cròniques. Unes de les afeccions més comunes i de les quals sovint se'n desconeix l'origen són les malalties inflamatòries intestinals. Segon un estudi publicat a mitjans del 2021 pel Centre d'Investigació Biomèdica en Xarxa de l'Institut de Salut Carlos III, que pertany al ministeri de Ciència i Innovació, normalment s'inicien durant la joventut i es van repetint en forma de brots un cop i un altre en el decurs de la vida de les persones afectades, sense que es coneguin les causes d'aquests rebrots. En paral·lel, fa més de dues dècades es va començar a estudiar la relació entre el sistema immunitari i el sistema nerviós. Diversos treballs pioners, realitzats a finals de la dècada de 1990, van demostrar que les terminacions nervioses que innerven els ganglis limfàtics contribueixen a regular la resposta immunitària. La funció d'aquests ganglis és filtrar les partícules estranyes, entre les quals hi ha bacteris i virus, i presentar-les als glòbuls blancs que hi ha dins els ganglis perquè iniciïn la resposta de defensa. Amb aquests precedents, la investigadora Asya Rolls i els seus col·laboradors, de diverses universitats i centres de recerca d'Israel i dels Estats Units, es van preguntar si hi ha cap relació entre les malalties inflamatòries cròniques, en què intervé el sistema immunitari, i el sistema nerviós. Segons han publicat recentment a la revista científica Cell, la inflamació de determinats teixits genera una empremta neuronal al cervell, de manera que si es tornen a activar les xarxes neuronals que mantenen la memòria de la inflamació inicial, encara que sigui per causes alienes al procés inflamatori, la resposta inflamatòria es torna a produir.

The HERC protein family is one of three subfamilies of Homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases. Six HERC genes have been described in humans, two of which encode Large HERC proteins -HERC1 and HERC2- with molecular weights above 520 kDa that are constitutively expressed in the brain. There is a large body of evidence that mutations in these Large HERC genes produce clinical syndromes in which key neurodevelopmental events are altered, resulting in intellectual disability and other neurological disorders like epileptic seizures, dementia and/or signs of autism. In line with these consequences in humans, two mice carrying mutations in the Large HERC genes have been studied quite intensely: the tambaleante mutant for Herc1 and the Herc2+/530 mutant for Herc2. In both these mutant mice there are clear signs that autophagy is dysregulated, eliciting cerebellar Purkinje cell death and impairing motor control. The tambaleante mouse was the first of these mice to appear and is the best studied, in which the Herc1 mutation elicits: (i) delayed neural transmission in the peripheral nervous system; (ii) impaired learning, memory and motor control; and (iii) altered presynaptic membrane dynamics. In this review, we discuss the information currently available on HERC proteins in the nervous system and their biological activity, the dysregulation of which could explain certain neurodevelopmental syndromes and/or neurodegenerative diseases., This work was funded by the following grants: EMP-V (DGICYT BFU2011-27207 and Spanish Junta de Andalucía CTS-2257); RR (Spanish Junta de Andalucía BIO-113 and SAF2015-64171-R); SB (Spanish Junta de Andalucía, Postdoctoral grant PAIDI-Doctor); JAA (Spanish Junta de Andalucía BIO-209 and DGICYT BFU2015-64536-R); JLR (Agencia Estatal de Investigación: PID2020-120344RB-I00 / MCIN / AEI / 10.13039/501100011033).

The availability of specific markers expressed in different regions of the developing nervous system provides a useful tool to illuminate their development, regulation and function. We have identified by expression profiling a putative non-coding RNA, Rmst, that exhibits prominent expression in the midbrain floor plate region, the isthmus and the roof plate of the anterior neural tube. At the developmental stage when the ventral dopaminergic neuron territory is being established, Rmst expression appears to be restricted to the presumptive dopaminergic neurons of the ventral tegmental area that lies close to the ventral midline. Thus this study presents Rmst as a novel marker for the developing dopaminergic neurons in the mesencephalic floor plate as well as a marker for the dorsal midline cells of the anterior neural tube and the isthmic organizer.

ilustraciones Resumen Henry Head en 1890 gracias a sus estudios sobre el herpes zoster, la distribución de los dolores referidos en enfermedades viscerales y los trastornos sensitivos en lesiones cerebrales, llego a determinar las áreas de los diversos territorios sensitivos periféricos, logrando realizar el primer mapa de dermatomas más completo de la historia (38). Definiendo además tres sensibilidades distintas del sistema nervioso, una sensibilidad profunda, una protopatica y otra epicrítica. (33) Por su parte James Mackenzie fue más conocido por los importantes avances en el estudio de la fisiología cardiaca en especial en la descripción de la fibrilación auricular y el fenómeno de la remodelación eléctrica (39). Estos autores británicos describieron cómo las enfermedades viscerales se manifiestan a través de la alteración sensitiva de los tejidos como la piel, el músculo y articulaciones, hallazgos que más adelante serían explicados por el fenómeno del metamerismo embriológico (12) y lo que explicaría la continuidad funcional y fisiopatológica que se observaba en la clínica. Así mismo, estos autores describieron cómo el sistema nervioso de alguna manera tenía un papel central en la coordinación de estos fenómenos abriendo la puerta para la posibilidad de influenciar estos estados patológicos viscerales desde sus correlaciones funcionales con los tejidos con quienes mantenían una conexión. El análisis comparativo ofrecerá un panorama para ahondar en las características y los fundamentos de esta escuela, aumentando la comprensión sobre una tendencia en la historia de la medicina que centra su teoría fisiopatológica sobre el sistema nervioso. (Texto tomado de la fuente) Abstract: Henry Head in 1890, thanks to his studies on herpes zoster, the distribution of referred pain in visceral diseases and sensory disorders in brain injuries, came to determine the areas of the various peripheral sensory territories, achieving the first map of most complete dermatomes in history (38). He also defined three different sensitivities of the nervous system, a deep sensitivity, a protopathic and an epicritic. (33) For his part, James Mackenzie was best known for the important advances in the study of cardiac physiology, especially in the description of atrial fibrillation and the phenomenon of electrical remodeling (39). These British authors described how visceral diseases are manifested through sensitive alteration of tissues such as skin, muscle and joints, findings that would later be explained by the phenomenon of embryological metamerism (12) and what would explain the functional continuity and pathophysiology observed in the clinic. Likewise, these authors described how the nervous system somehow had a central role in the coordination of these phenomena, opening the door for the possibility of influencing these visceral pathological states from their functional correlations with the tissues with which they maintained a connection. The comparative analysis will offer an overview to delve into the characteristics and foundations of this school, increasing the understanding of a trend in the history of medicine that focuses its pathophysiological theory on the nervous system. Maestría Magíster en Medicina Alternativa Articulo de revisión. Estudio histórico-descriptivo en donde se realizará un análisis teórico y conceptual sobre las escuelas de fisiología del Nervismo ruso y sobre las teorías desarrolladas por representantes de la escuela británica con propuestas centradas en el sistema nervioso.

Nervous systems are complex cellular structures that allow animals to interact with their environment, which includes both the external and the internal milieu. The astonishing diversity of nervous system architectures present in all animal clades has prompted the idea that selective forces must have shaped them over evolutionary time. In most cases, neurons seem to coalesce into specific (centralized) structures that function as “central processing units” (CPU): “brains.” Why did neural systems adopt this physical configuration? When did it first happen? What are the physiological, computational, and/or structural advantages of concentrating many neurons in a specific place within the body? Here we examine the concept of nervous system centralization and factors that might have contributed to the evolutionary success of this centralization strategy. In particular, we suggest a putative scenario for the evolution of neural system centralization that incorporates different strands of evidence. This scenario is based on some premises: (1) Receptors originated before neurons (sensors before transmitters) and there were deployed in the first organisms in an asymmetric fashion (deposited randomly in the outer layer); (2) Receptors were segregated in a preferential position in response to an anisotropic environment, (3) Neurons were born in association with this receptors and used to transmit signals distally; (4) Energetics preferentially selected the localization of neurons, and synapsis, close to the receptors (to minimize wire use, for instance); (5) The presence of condensed areas of neurons could have stimulated the proliferation of more receptors in the vicinity, increasing the repertoire of signals processed in an specific body domain (i.e., head) plus contributing to amplify the computational power of the neuronal aggregate; (6) The proliferation of receptors would have induced the proliferation of more neurons in the aggregate, with a further increase in its computational power (hence, diversifying the behavioral repertoire). These last two steps of proliferation and aggregation could have been sustained through a feedback loop, reiterated many times, generating distinct topologies in different lineages. Our main aim in this paper is to examine the brain as both a biological and a physical or computational device.

Pòster Juny

Motorincompetence in adolescence has a very direct association with physical inactivity and increased risk of injury. The aim of this study is focused in two parts: analyze Fundamental Motor Skills in teenagers and study the effects of an Integrative Neuromuscular Training program. In this way, we will answerthe hypothesis ofthe study evaluating if this type of program can improve the level in motor skills and sports performance in young people, in order to bring them to an active and healthy lifestyle. To carry out this project, data has been collected from a total of 58 studentsfrom 1r ESO in the high school Vall de Llémena, from a descriptive study, the level of motor competence is analyzed in relation to sex, age of maturity and their live style. The results indicate thatthe boys have betterlevels of Motor Competence than girls, also the period of growth development is determinant, because the students who are in pre-puberty stage show the bests results indicating that having an active live style is essential. From here it has been proposed the idea of introduce an Integrative Neuromuscular Training in the warm-up in order to evaluate the effects and contribute to correct and improve her motor skills La incompetència motriu en l’adolescència té una associació molt directe pel que fa a la inactivitat física i l’augment dels riscs de lesions. L’objectiu general d’aquest estudi es centra amb dues parts: analitzar les Habilitats Motrius Bàsiques dels adolescents i estudiar els efectes d’un programa de Treball Neuromuscular Integrat. D’aquesta manera donarem resposta a la hipòtesi de l’estudi, valorant si aquest tipus de programa pot afavorir en la millora del nivell de les Habilitats Motrius i en el rendiment esportiu dels joves, per tal de poder portar-los a un estil de vida actiu i saludable. Per dur a terme aquest projecte, s’han recollit les dades d’un total de 58 alumnes del 1r cicle de secundària de l’Institut Vall de Llémena. A partir d’un estudi descriptiu,s’analitza el nivell de CM en relació amb el sexe, l’edat madurativa i el seu estil de vida. Els resultats obtinguts indiquen que, els nois presenten millors nivells de competència motriu que les noies, que el període de desenvolupament és determinant, ja que els alumnes que estan en l’etapa prepuberal mostren els millors resultats afegint també que portar un estil de vida actiu és essencial. A partir d’aquí es proposa la idea d’implementar un TNI dins l’escalfament d’Educació Física i així poder valorar els seus efectes i contribuir en rectificar i polir les seves Habilitats Motrius

To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type–specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease., Data was generated as part of the PsychENCODE Consortium, supported by MH103339, MH106934, and MH110926. Additional support was provided by NIH grants MH109904, MH106874, AG048918, DK111178, and NS092988 (National Chimpanzee Brain Resource), the Kavli Foundation, the James S. McDonnell Foundation, NSF grant BCS-1316829, MINECO BFU2014-55090-P (FEDER), Howard Hughes International Early Career, and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya.

Genetic factors involved in the susceptibility to drug addiction still remain largely unknown. MiRNAs seem to play key roles in the drug-induced plasticity of the brain that likely drives the emergence of addiction. In this work we explored the role of miRNAs in drug addiction. With this aim, we selected 62 SNPs located in the 3’UTR of target genes that are predicted to alter the binding of miRNA molecules and performed a case-control association study in a Spanish sample of 735 cases (mainly cocaine-dependent subjects with multiple drug dependencies) and 739 controls. We found an association between rs1047383 in the PLCB1 gene and drug dependence that was replicated in an independent sample (663 cases and 667 controls). Then we selected 9 miRNAs predicted to bind the rs1047383 region, but none of them showed any effect on PLCB1 expression. We also assessed two miRNAs binding a region that contains a SNP in linkage disequilibrium with rs1047383, but although one of them, hsa-miR-582, was found to downregulate PLCB1, no differences were observed between alleles. Finally, we explored the possibility that PLCB1 expression is altered by cocaine and we observed a significant upregulation of the gene in the nucleus accumbens of cocaine abusers and in human dopaminergic-like neurons after cocaine treatment. Our results, together with previous studies, suggest that PLCB1 participates in the susceptibility to drug dependence.

The activation of N-Methyl D-Aspartate Receptor (NMDAR) by glutamate is crucial in the nervous system function, particularly in memory and learning. NMDAR is composed by two GluN1 and two GluN2 subunits. GluN2B has been reported to participate in the prevalent NMDAR subtype at synapses, the GluN1/2A/2B. Here we studied the regulation of GluN2B expression in cortical neurons finding that glutamate up-regulates GluN2B translation through the action of nitric oxide (NO), which induces the phosphorylation of the eukaryotic translation initiation factor 2 α (eIF2α). It is a process mediated by the NO-heme-regulated eIF2α kinase (HRI), as the effect was avoided when a specific HRI inhibitor or a HRI small interfering RNA (siHRI) were used. We found that the expressed GluN2B co-localizes with PSD-95 at the postsynaptic ending, which strengthen the physiological relevance of the proposed mechanism. Moreover the receptors bearing GluN2B subunits upon NO stimulation are functional as high Ca2+ entry was measured and increases the co-localization between GluN2B and GluN1 subunits. In addition, the injection of the specific HRI inhibitor in mice produces a decrease in memory retrieval as tested by the Novel Object Recognition performance. Summarizing our data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons. This work was supported by the Plan Estatal de I+D+I 2013-2016 and the ISCIII-Subdirección/nGeneral de Evaluación y Fomento de la Investigación (Grants PI13/00408; PI13/00135; Red HERACLES RD12/0042/0014) and FEDER Funds; the Spanish Ministry of Economy and Competitiveness (SAF2014-52228-R; SAF2015-69762-R; BFU2015-68568-P); MINECO (PCIN-2014-105); Fundació la Marató de TV3 (20134030 and 20140210); FONDECYT 3140355 (ERF),/n1120512 (AAR) and 3120015 (LVR)

OptoGluNAM4.1, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 4 (mGlu4) contains a reactive group that covalently binds to the receptor and a blue-light-activated, fast-relaxing azobenzene group that allows reversible receptor activity photocontrol in vitro and in vivo. OptoGluNAM4.1 induces light-dependent behavior in zebrafish and reverses the activity of the mGlu4 agonist LSP4-2022 in a mice model of chronic pain, defining a photopharmacological tool to better elucidate the physiological roles of the mGlu4 receptor in the nervous system. © 2016 Elsevier Ltd, We are grateful to C. Serra, L. Muñoz, J. Hernando, F. Malhaire, Y. Pérez, M. Izquierdo-Serra, F. Aguado, S. Laffray, E. Bourinet, F.Codony (GenIUL), and Y. Chomis (Viewpoint) for helpful discussions and technical support. A.F. is supported by a Fondation Lefoulon Delalande postdoctoral fellowship , C.J. by a grant from INSERM ATIP-AVENIR and Marie Curie CIG ( PCIG12-GA-2012-332772 ). A.F. and C.J. are members of the Laboratory of Excellence Ion Channel Science and Therapeutics supported by a grant from the ANR . J.-P.P. is a member of the Laboratory of Excellence Epingenmed. We acknowledge financial support from the European Union's Seventh Framework Program for research, technological development, and demonstration under grant agreements 270483 (Focus), 210355 (Opticalbullet), and 335011 (Theralight) to P.G.; the Federation of European Biochemical Societies ; the Catalan government ( 2012FI_B 01122 to S.P., 2014SGR-1251 to P.G., and 2014SGR-0109 to A. Llebaria); the Spanish Government ( SAF2014-58396-R to J.G., CTQ2014-57020-R to A.L., and CTQ2013-43892R to P.G.); the ERANET Neuron LIGHTPAIN project (to A.L., J.G., and J.-P.P.); the Ramón Areces Foundation , the ERANET SynBio Modulightor project (to P.G.); the HBP Wavescales project (to P.G.); the Fondation Recherche Médicale (FRM team DEQ20130326522 to J.P.P.); the Agence Nationale de la Recherche ( ANR-13-BSV1-006 to C.G.) and the Beatriu de Pinós program of Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) for the support of X.R.

Through somatic exocytosis neurons liberate immense amounts of transmitter molecules that modulate the functioning of the nervous system. A stream of action potentials triggers an ATP-dependent transport of transmitter-containing vesicles to the plasma membrane, that ends with a large-scale exocytosis. It is commonly assumed that biological processes use metabolic energy with a high thermodynamic efficiency, meaning that most energy generates work with minor dissipation. However, the intricate ultrastructure underlying the pathway for the vesicle flow necessary for somatic exocytosis challenges this possibility. To study this problem here we first applied thermodynamic theory to quantify the efficiency of somatic exocytosis of the vital transmitter serotonin. Then we correlated the efficiency to the ultrastructure of the transport pathway of the vesicles. Exocytosis was evoked in cultured Retzius neurons of the leech by trains of 10 impulses delivered at 20 Hz. The kinetics of exocytosis was quantified from the gradual fluorescence increase of FM1-43 dye as it became incorporated into vesicles that underwent their exo-endocytosis cycle. By fitting a model of the vesicle transport carried by motor forces to the kinetics of exocytosis, we calculated the thermodynamic efficiency of the ATP expenses per vesicle, as the power of the transport divided by total energy ideally produced by the hydrolysis of ATP during the process. The efficiency was remarkably low (0.1–6.4%) and the values formed a W-shape distribution with the transport distances of the vesicles. Electron micrographs and fluorescent staining of the actin cortex indicated that the slopes of the W chart could be explained by the interaction of vesicles with the actin cortex and the calcium-releasing endoplasmic reticulum. We showed that the application of thermodynamic theory permitted to predict aspects of the intracellular structure. Our results suggest that the distribution of subcellular structures that are essential for somatic exocytosis abates the thermodynamic efficiency of the transport by hampering vesicle mobilization. It is remarkable that the modulation of the nervous system occurs at the expenses of an efficient use of metabolic energy. Copyright © 2019 Noguez, Rubí and De-Miguel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies.

El desenvolupament mental dels infants es veu influenciat per l'ambient on creixen i s'eduquen. Hi ha dades que indiquen que la presència d'espais verds pot millorar-ne el desenvolupament cognitiu, però fins ara no s'havia fet cap estudi que avalués aquesta qüestió amb perspectiva temporal, és a dir, des del naixement. Un equip de recerca encapçalat pels investigadors Jordi Sunyer, Ferran Ballester i Jesús Ibarlueza, d'unes quantes universitats i centres de recerca catalans, espanyols, holandesos i italians, ha avaluat l'efecte dels espais verds sobre la maduració de la capacitat de mantenir l'atenció durant l'educació infantil i l'inici de la primària. Els resultats, que han publicat a la revista Environmental Health Perspectives, indiquen que els infants que viuen des del naixement en indrets amb espais verds obtenen més bons resultats en proves que avaluen la capacitat de mantenir l'atenció focalitzada, cosa que hauria de ser tinguda en compte quan s'estableixen polítiques municipals d'ordenació territorial.

We describe the data processing employed to match EMG signals with the categorized behavioral movements obtained from video recordings in awake rats while reaching and grasping pellets. We want to determine whether or not, the forelimb muscles follow a temporal synchronized pattern of activity during reaching and grasping. Data processing included raw data filtering and obtaining the first derivate. We found consistency in this procedure between attempts, indicating the utility for studying the brain to spinal cord function underlying volitional and skilled movements in the rat.

Pòster Juny

11 pages, 6 figures, supplementary material https://doi.org/10.1038/s41598-018-32709-3, Traditionally, the internal morphology of crustacean larvae has been studied using destructive techniques such as dissection and microscopy. The present study combines advances in micro-computed tomography (micro-CT) and histology to study the internal morphology of decapod larvae, using the common spider crab (Maja brachydactyla Balss, 1922) as a model and resolving the individual limitations of these techniques. The synergy of micro-CT and histology allows the organs to be easily identified, revealing simultaneously the gross morphology (shape, size, and location) and histological organization (tissue arrangement and cell identification). Micro-CT shows mainly the exoskeleton, musculature, digestive and nervous systems, and secondarily the circulatory and respiratory systems, while histology distinguishes several cell types and confirms the organ identity. Micro-CT resolves a discrepancy in the literature regarding the nervous system of crab larvae. The major changes occur in the metamorphosis to the megalopa stage, specifically the formation of the gastric mill, the shortening of the abdominal nerve cord, the curving of the abdomen beneath the cephalothorax, and the development of functional pereiopods, pleopods, and lamellate gills. The combination of micro-CT and histology provides better results than either one alone, Financial support was provided by the Spanish Ministry of Economy and Competitiveness through the INIA project (grant number RTA2011-00004-00-00) to G.G. and a pre-doctoral fellowship to D.C. (FPI-INIA)

Curs 2016-2017, La finalitat d’aquest treball és veure com són els esquemes mentals dels alumnes en els diversos cicles de Primària sobre el sistema nerviós. Aquesta investigació es realitza mitjançant un qüestionari en què els alumnes han de plasmar les seves idees intuïtives sobre el tema sigui dibuixant o fent una explicació del funcionament. Així doncs, en els resultats podem veure l’evolució dels models mentals dels alumnes al llarg de la Primària i podem identificar en quins aspectes cal fer-hi més èmfasi. En tots els cicles hi ha la presència de les mateixes entitats tot i que segons el temari que es fa a cada cicle es distingeixen diverses parts dins el sistema nerviós. Els nervis que hi ha al cos, no és un aspecte que tenen clar els infants i per tant, s’hauria de modelitzar en les pròximes intervencions. En conclusió, l’estudi mostra com la idea de sistema nerviós no és del tot clara en els tres cicles de Primària, ja que no es treballa en profunditat fins a finals de 6è., The purpose of this project is to observe the mental scheme of children from different cycles in a Primary School, in order to know about the Nervous System. This research is done through a questionnaire in which students have to express their intuitive ideas either drawing or explaining its function. Therefore, in the results, we can see the evolution of mental schemes of the students throughout the Primary School and we can identify which aspects need more emphasis. In all courses, there are presences of the same entities, but depending on the syllabus that is done in each cycle, we can differentiate various parts of the nervous system. The nerves are one aspect that it is not clearly understood by the students, and for this reason it should be modeled in the next interventions. In conclusion, this project shows how the idea of the nervous system is not clear in the three courses of Primary, because they do not work deeply with this topic until they are in the sixth grade.

During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies. Considering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12 Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity., Highlights • Resting-state MEG reveals correlated amplitude envelopes between brain areas. • Envelope functional connectivity spans a range of carrier frequencies. • Local emergence of carrier oscillations modeled with a Hopf bifurcation model. • Each brain area may resonate at one or multiple fundamental frequencies. • Multiple resonant frequencies outperform the single frequency scenario., Graphical abstract fx1

Pòster Juny

The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating the membrane potential, facilitates downstream Ca2+ -dependent pathways and becomes concentrated in specific membrane microdomains that serve as signaling platforms. Increased and/or delocalized expression of the channel is observed at the onset of several autoimmune diseases. In this work, we show that adenosine (ADO), which is a potent endogenous modulator, stimulates PKC, thereby causing immunosuppression. PKC activation triggers down-regulation of Kv1.3 by inducing a clathrin-mediated endocytic event that targets the channel to lysosomal-degradative compartments. Therefore, the abundance of Kv1.3 at the cell surface decreases, which is clearly compatible with an effective anti-inflammatory response. This mechanism requires ubiquitination of Kv1.3, catalyzed by the E3 ubiquitin-ligase Nedd4-2. Postsynaptic density protein 95 (PSD-95), a member of the MAGUK family, recruits Kv1.3 into lipid-raft microdomains and protects the channel against ubiquitination and endocytosis. Therefore, the Kv1.3/PSD-95 association fine-tunes the anti-inflammatory response in leukocytes. Because Kv1.3 is a promising multi-therapeutic target against human pathologies, our results have physiological relevance. In addition, this work elucidates the ADO-dependent PKC-mediated molecular mechanism that triggers immunomodulation by targeting Kv1.3 in leukocytes.

[eng] In the brain events happen in the scale of milliseconds, and the fine processes of neurons and neuroglia are highly compartmentalized at a microscopic level. These exclusive features of the brain define extremely precise temporal and spatial patterns of cellular activity, which are of fundamental importance for its proper functioning, because they allow the fast processing, sorting, integration, and flow of information with high reproducibility and precision. To gain deeper understanding of how these patterns are organized in time and space, we need new tools that overcome the spatiotemporal limitations of the currently available techniques. Recently, neurobiology was revolutionized by the idea of using light to control neuronal proteins remotely with millisecond- and micrometer-precision, which led to the development of a new field of study called optogenetics. After more than a decade, the control of protein function with light has gone far beyond optogenetics and its need of genetic manipulations. Optopharmacology is now gaining importance because it is less invasive and suitable for controlling endogenous proteins with light, and each year compounds with enhanced photochemical and pharmacological properties are developed. This thesis reviews the optopharmacological tools developed so far to study a family of neuronal proteins called metabotropic glutamate (mGlu) receptors. We are interested in these proteins because they participate in neurotransmission, and are link to neuropathologies when dysfunctional. Thanks to pioneering advances in probing these receptors with light, many features of mGlu signaling have been unraveled, and it is now emerging that these receptors follow activation mechanisms different from those initially foreseen. Still, it is not clear what their exact kinetics are, or which are the functional consequences of temporal and spatial patterns of activity – which are widespread both among brain structures and across evolution. Despite the fundamental relevance of mGlu receptors to brain computing in physiology and disease, the mechanisms that govern their functioning are still partially understood, and this is mainly due to the scarcity of tools to activate mGlu receptors with spatiotemporal precision. The aim of this thesis was to expand the toolbox of optical switches to activate with light mGlu receptors, with special interest in respecting the physiological context of their activation. For that purpose, we discarded approaches based on genetic engineering of receptors, as well as irreversible uncaging of compounds. We preferred the use of optopharmacology, and specifically applied it to allosteric modulators, which display higher selectivity and more physiological activation than orthosteric ligands. This objective implied technical challenges due to the structural restrictions of mGlu allosteric binding pockets, but at the same time offered high gains to spatiotemporally control these receptors both in therapeutic and basic research applications. From these premises, we: 1. developed the first light-regulated allosteric modulators targeting metabotropic glutamate receptors. The molecular design, in vitro and in vivo characterization of alloswitch-1 and G4optoNAM are presented in Chapters 1-2. 2. expanded the knowledge about this new class of compounds through a library of compounds derived from alloswitch-1, and present the inferred data about structure-activity relationship and optimal optopharmacological characteristics for allosteric photoswitches of mGlu receptors (Chapter 3). 3. demonstrated the functional photoisomerization of alloswitch-1 by using two-photon stimulation, with the aim of exploring the resolution limits of reversible optical switches (Chapter 4). Overall, this thesis shows for the first time the design and characterization of optical switches for the allosteric and remote control of endogenous mGlu receptors in vitro and in vivo with light. This advance broadens the availability of optical tools in research to manipulate mGlu receptors with high temporal and spatial resolution, and represents a step forward in innovative opportunities to treat neuropathologies with light., [cat] En el sistema nerviós els esdeveniments es desenvolupen en l’escala temporal dels milisegons, i els processos que tenen lloc en neurones i cèl·lules de la glia presenten compartimentalitzacions microscòpiques. Aquesta organització determina uns patrons d’activitat ben definits temporal i espacialment, els quals permeten el precís funcionament del sistema nerviós per tal de transmetre, integrar i processar la informació d’una forma rapida i especifica. Per entendre millor el modus operandi del cervell en el temps i l’espai, calen noves eines que permetin superar les limitacions espaitemporals de les tecnologies existents per l’observació passiva o l’activa manipulació del sistema nerviós. Una de les estratègies més rapides i precises per activar e inactivar proteïnes neuronals es basa en la seva fotosensibilització, per tal de poder-les controlar mitjançant la precisió espai-temporal incomparable que la llum ofereix. Aquesta tesi fa un resum de les eines òptiques disponibles per detectar (sensors) e induir (commutadors) l’activitat d’una família de proteïnes neuronals denominades receptors metabotropics de glutamat (mGlu). Estem interessats en aquests receptors per la importància que tenen com moduladors de la neurotransmissió, i el seu rol en el desenvolupament de neuropatologies. L’objectius de la tesi fou desenvolupar eines optofarmacològiques pel control òptic i reversible dels receptors mGlu amb llum, considerant els grans avantatges d’especificitat espaitemporal que ofereix el fotocontrol de proteïnes i l’escassetat de tals eines. El primer capítol descriu el disseny, la síntesi i la caracterització d’alloswitch-1, el primer fotocommutador al·lostèric capaç d’activar receptors mGlu amb llum de forma reversible. El segon capítol il·lustra la caracterització de G4optoNAM, un fotocommutador al·lostèric actiu en receptors mGlu4. El tercer capítol recull una llibreria de compostos derivats del precursor alloswitch-1 amb diverses substitucions químiques, que presenten característiques fotofísiques i optofarmacològiques variades. Al quart i últim capítol demostrem la capacitat dels alloswitches de fotoisomeritzar amb il·luminació micromètrica amb un làser multifotó. La nostra capacitat d’expandir el ventall d’eines optofarmacològiques que permeten un control farmacològic de receptors neuronals amb llum, de forma remota i no invasiva, ha aportat a la comunitat científica noves metodologies farmacològiques per a l’estudi de la fisiopatologia del sistema nerviós.

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare disease characterized by the deposition of multiple intracytoplasmic neuronal inclusions that contain mutated neuroserpin. Tg-Syracuse (Tg-Syr) mice express Ser49Pro mutated neuroserpin and develop clinical and neuropathological features of human FENIB. We used 8-, 34-, 45- and 80-week-old Tg-Syr mice to characterize neuroinflammation and the unfolded protein response (UPR) in a neurodegenerative disease in which abnormal protein aggregates accumulate within the endoplasmic reticulum (ER). There were scattered neuroserpin inclusions in Tg-Syr mice at 8 weeks of age; the numbers of neurons involved and the amount of neuroserpin per neuron increased with age throughout the CNS to 80 weeks of age; no similar inclusions were found in wild type (Tg-WT) mice at any age. Increases in numbers of astrocytes and microglia occurred at advanced disease stages. Among 22 markers in 80-week-old Tg-Syr mice, only II1b and II10rb mRNAs in the somatosensory cortex and CxCl10 and Il10rb mRNAs in the olfactory bulb were upregulated when compared with Tg-WT mice indicating a limited relationship between neuroserpin inclusions and inflammatory responses. The changes were accompanied by a transient increase in expression of Xbp1 spliced at 45 weeks and increased ERdJ4 mRNAs at 80 weeks. The sequestration of UPR activators GRP78 and GRP94 in neuroserpin inclusions might explain the limited UPR responses despite the accumulation of neuroserpin in the ER in this FENIB mouse model.

Introduction Several studies on cadavers dissection have shown that collateral branches of the trigeminal nerve cross muscle bundles on their way, being a possible etiological factor of some nerve disturbances. Case Report A 45-year-old man attended to the Temporomandibular Joint and Orofacial Pain Unit of the Master of Oral Surgery and Implantology in Hospital Odontològic of Barcelona University, referring tingling in the left hemifacial región and ipsilateral lingual side for one year, with discomfort when shaving or skin compression. Discussion Several branches of the trigeminal nerve follow a path through the masticatory muscles, being the lingual nerve and buccal nerve the most involved. The hyperactivity of the muscle bundles that are crossed by nerve structures generates a compression that could explain certain orofacial neuropathies (numbness and / or pain) in which a clear etiologic factor can not be identified. Key words:Buccal nerve, paresthesia, idiopathic trigeminal sensory neuropathy.

Chimera states, namely the coexistence of coherent and incoherent behavior, were previously analyzed in complex networks. However, they have not been extensively studied in modular networks. Here, we consider the neural network of the \textit{C.elegans} soil worm, organized into six interconnected communities, where neurons obey chaotic bursting dynamics. Neurons are assumed to be connected with electrical synapses within their communities and with chemical synapses across them. As our numerical simulations reveal, the coaction of these two types of coupling can shape the dynamics in such a way that chimera-like states can happen. They consist of a fraction of synchronized neurons which belong to the larger communities, and a fraction of desynchronized neurons which are part of smaller communities. In addition to the Kuramoto order parameter $\rho$, we also employ other measures of coherence, such as the chimera-like $\chi$ and metastability $\lambda$ indices, which quantify the degree of synchronization among communities and along time, respectively. We perform the same analysis for networks that share common features with the \textit{C.elegans} neural network. Similar results suggest that under certain assumptions, chimera-like states are prominent phenomena in modular networks, and might provide insight for the behavior of more complex modular networks., Comment: 10 pages, 3 figures

La variabilitat de la freqüència cardíaca (VFC) fa referència al temps de l'interval entre batec i batec del cor. Aquest interval no és fix, sinó que oscil·la constantment i la dinàmica d'aquestes oscil·lacions, juntament amb una anàlisi matemàtica adequada, pot aportar una informació molt valuosa sobre l'equilibri del Sistema Nerviós Autònom (SNA) com a responsable del funcionament del cor.L'anàlisi de la VFC aporta informació sobre qualsevol situació que trenqui l'equilibri homeostàtic en el nostre organisme, és per això que s'estudia la seva variació en algunes condicions associades amb la presència de certes patologies. A l'àmbit de l'entrenament dels esports, donat que l'exercici físic és un agent promotor de l'estrès fisiològic, els canvis de la VFC s'han associat a l'assimilació de les càrregues d'entrenament o certes condicions vinculades a la síndrome de sobreentrenament.Els avenços tecnològics han aportat solucions per analitzar la VFC, en aquest sentit es presenten diferents opcions de software científic per analitzar en profunditat la dinàmica de la VFC, així com diverses opcions d'aplicacions per a dispositius mòbils que cada cop més ocupen aquest espai en el món de l'entrenament esportiu.

Objectives Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF. Methods The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF. Results The frequency of the haplotype C-C (rs645649–rs582262) was significantly increased in patients compared to controls (P = 0.0043), while the haplotype T-C-C-T-C-A (rs3763180–rs10484320–rs4960155–rs9379002–rs9405890–rs1475157) was more frequent in controls (P = 3.1 × 10−5). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P = 0.005). Conclusions Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF. We are grateful to all the participants, whose willingness to take part made this work possible. We also thank Anna Valldeperas for her participation in molecular laboratory tasks. Funding for this study was provided by: i) Centro de Investigación en Red de Salud Mental (CIBERSAM), ii) Fundación Alicia Koplowitz; iii) Ministry of Science and Innovation (PIM2010ERN-00642)-ERA-NET NEURON; iv) P1·1B2010-40 and P1·1B2011-47 from the Fundació Bancaixa-UJI; v) Miguel Servet Research Contracts (CP10/00596) from the Plan Nacional de I + D+i and co-funded by the Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación and the European Regional Development Fund (FEDER); vi) Health research funds from the Spanish Government (PI11/01977); vii) METSY project of the 7th Framework Programme of the European Commission (FP7-HEALTH-602478) and Ministry of Economy and Competitiveness (PI10/01920, PI14/02096); Claudia Prats was supported by APIF-IBUB grant 2014. Thanks to the Comissionat per a Universitats i Recerca del DIUE (2014SGR1636, 2014SGR1573, 2014SGR489).

L’alteració en el moviment de l’extremitat superior (ES) és una de les manifestacions més freqüents de l’ictus, cursant amb pèrdua de la força muscular, de la fluïdesa i capacitat de fragmentació entre les articulacions així com amb alteracions sensitives tàctils i propioceptives o bé, cognitives de l’atenció, capacitat per imaginar, etc. L’actuació terapèutica s’ha adaptat a l’actual concepte de moviment fruit del funcionament sistèmic de les estructures nervioses, amb la integració d’informacions de caire motor, sensitiu i cognitiu per la consecució del moviment coordinat i funcional. L’abordatge neurocognitiu insereix estratègies cognitives com l’observació de l’acció, la imatge motora o la imitació en els exercicis terapèutics, juntament amb l’activació guiada de l’atenció o la resolució de problemes per la recuperació del moviment post-ictus. L’objectiu principal consisteix en avaluar l’efectivitat de l’activació guiada dels processos cognitius cap a les informacions del cos i de la interacció cos-objecte per la millora de la quantitat i la qualitat del moviment de l’ES en pacients d’ictus en fase subaguda. S’ha procedit a revisar publicacions científiques amb els criteris de selecció i filtres establerts, a través de diferents cerques, utilitzant bases de dades bibliogràfiques com Science Direct, Pubmed, PEDro o The Cochrane Library. S’ha dissenyat un protocol de valoració i tractament basat en l’abordatge neurocognitiu i en els avenços actuals en neurociències per la recuperació del moviment de l’ES en ictus subagut. El protocol s’ha aplicat en el marc d’un estudi pilot experimental aleatoritzat de simple cec realitzat durant els anys 2012-13 en el Departament de Rehabilitació de l’Hospital Universitari Germans Trias i Pujol de Badalona en 8 participants. Aquests es van distribuir en el grup control, que seguien el protocol tradicional, i el grup experimental amb l’aplicació del protocol neurocognitiu. L’estudi pilot ha avaluat: 1) l’evolució del participant en les diferents avaluacions per cada variable: motora (funcionalitat i força muscular), sensitiva (tacte i cinestèsia) i cognitiva (imatge motora); 2) l’evolució en el temps comparant entre grups i 3) la viabilitat del protocol neurocognitiu en un context real. S’ha realitzat un anàlisi descriptiu i estadístic amb tests no paramètrics com els tests U Mann-Whitney i Wilcoxon signed-rank. Posteriorment, el protocol neurocognitiu ha estat avaluat per un panell d’experts mitjançant el mètode Delphi per tal d’obtenir un consens i millores per futures aplicacions. S’han obtingut dues revisions bibliogràfiques: la primera sobre l’organització motora cortical i el rol dels sistemes de les neurones mirall i la segona referent a la fisioteràpia neurocognitiva. S’ha obtingut un protocol de valoració i tractament amb l’utilització de 4 instruments de mesura per les diferents variables així com una sèrie d’exercicis terapèutics organitzats jeràrquicament en funció de l’estat del participant. Els resultats indiquen una tendència clínica més favorable en el grup neurocognitiu, tot i que no estadísticament significativa, amb millores considerables en la capacitat funcional de l‘ES, i de forma més evident, a la mà. De l’aplicació del protocol en l’estudi pilot i de les aportacions dels experts emergeixen propostes de futur dirigides a: incrementar la mostra i el temps de la intervenció, realitzar estudis en ictus en fase crònica; efectuar una estratificació basal per establir correlacions entre variables; reorganitzar el temps de tractament segons l’estat inicial així com introduir tasques de discriminació d’altres informacions somatosensorials. El protocol neurocognitiu ha estat viable i sembla ser efectiu per afavorir una millor funcionalitat de l’ES del pacient amb ictus subagut, a través d’una avaluació acurada del seu estat per una millor adequació de l’exercici terapèutic en els aspectes que conformen el control motor. A més, l’alt grau de consens obtingut dels experts reforça el protocol per ser aplicat en futurs estudis sobre la fisioteràpia neurocognitiva.

Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation, whereas Wnt-3 enhanced SCNP proliferation transiently and increased neurogenesis through β-catenin signaling. Consistent with this, Wnt-3a and Wnt-3 differently regulate the expression of Cyclin-dependent kinase inhibitors. Furthermore, Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through ß-catenin and TCF4-dependent transcription. GSK-3ß inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies., Human Frontiers Science Program (HFSP) Ref. RGP0018/2007-C, the European Community’s RGP0018/2007-C (FP7/2007-2013) under grant agreement PITN-GA-2009-238242—DISCHROM project and grant agreement 278486-DEVELAGE, the Instituto de Salud Carlos III—Ministerio de Sanidad y Consumo Proyecto FIS (Fondo Investigación Sanitaria, Spain) through the E-RARE EuroRETT network, Grants P50-AG16573, HD065160-01 and SAF2007-6-8, the Fondation Lejeune, Botin Foundation, Fundació Agrupació Premi Àmbit Gent Grant and the Cellex Foundation (Catalonia

Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients' antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients' antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients' or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients' cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days 13-18), that after acid extraction and characterization with GluN1-expressing human embryonic kidney cells were confirmed to be against the NMDAR. Confocal microscopy and immunoblot analysis of the hippocampus showed progressive decrease of the density of total and synaptic NMDAR clusters and total NMDAR protein concentration (maximal on Day 18), without affecting the post-synaptic density protein 95 (PSD95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These effects occurred in parallel with memory and other behavioural deficits and gradually improved after Day 18, with reversibility of symptoms accompanied by a decrease of brain-bound antibodies and restoration of NMDAR levels. Overall, these findings establish a link between memory and behavioural deficits and antibody-mediated reduction of NMDAR, provide the biological basis by which removal of antibodies and antibody-producing cells improve neurological function, and offer a model for testing experimental therapies in this and similar disorders. This work was supported by the National Institutes of Health RO1NS077851 (J.D.), RO1MH094741 (R.B-G. and J.D.), Fundació La Marató de TV3 #101530 (J.D.), Fondo de Investigaciones Sanitarias/Instituto Carlos III (FIS PI11/01780 J.D.), ErasmusMC fellowship (M.T.), and Forschungsförderungsfonds Hamburg-Eppendorf FL)

The neurokinin 1 receptor (NK-1R) is the main receptor for the tachykinin family of peptides. Substance P (SP) is the major mammalian ligand and the one with the highest affinity. SP is associated with multiple processes: hematopoiesis, wound healing, microvasculature permeability, neurogenic inflammation, leukocyte trafficking, and cell survival. It is also considered a mitogen, and it has been associated with tumorigenesis and metastasis. Tachykinins and their receptors are widely expressed in various human systems such as the nervous, cardiovascular, genitourinary, and immune system. Particularly, NK-1R is found in the nervous system and in peripheral tissues and are involved in cellular responses such as pain transmission, endocrine and paracrine secretion, vasodilation, and modulation of cell proliferation. It also acts as a neuromodulator contributing to brain homeostasis and to sensory neuronal transmission associated with depression, stress, anxiety, and emesis. NK-1R and SP are present in brain regions involved in the vomiting reflex (the nucleus tractus solitarius and the area postrema). This anatomical localization has led to the successful clinical development of antagonists against NK-1R in the treatment of chemotherapy-induced nausea and vomiting (CINV). The first of these antagonists, aprepitant (oral administration) and fosaprepitant (intravenous administration), are prescribed for high and moderate emesis.

The proper growth and elaboration of neural processes is essential for the establishment of a functional nervous system during development and is an integral feature of neural plasticity throughout life. Nuclear factor-kappa B (NF-kappa B) is classically known for its ubiquitous roles in inflammation, immune and stress-related responses and regulation of cell survival in all tissues, including the nervous system. NF-kappa B participation in other cellular processes remains poorly understood. Here we report a mechanism for controlling the growth of neural processes in developing peripheral and central neurons involving the transcription factor NF-kappa B. Inhibiting NF-kappa B activation with super-repressor I kappa B-alpha, BAY 11 7082 (I kappa B-alpha phosphorylation inhibitor) or N-acetyl-Leu-Leu-norleucinal (proteosomal degradation inhibitor), or inhibiting NF-kappa B transcriptional activity with kappa B decoy DNA substantially reduced the size and complexity of the neurite arbors of sensory neurons cultured with brain-derived neurotrophic factor while having no effect on their survival. NF-kappa B exerted this effect during a restricted period of development following the phase of naturally occurring neuronal death when the processes and connections of the remaining neurons are extensively modified and refined. Inhibiting NF-kappa B activation or NF-kappa B transcriptional activity in layer 2 pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic arbor size and complexity. This function of NF-kappa B has important implications for neural development and may provide an explanation for reported involvement of NF-kappa B in learning and memory.

It is assumed that DNA sequences are conserved in the diverse cell types present in a multicellular organism like the human being. Thus, in order to compare the sequences in the genome of DNA from different individuals, nucleic acid is commonly isolated from a single tissue. In this regard, blood cells are widely used for this purpose because of their availability. Thus blood DNA has been used to study genetic familiar diseases that affect other tissues and organs, such as the liver, heart, and brain. While this approach is valid for the identification of familial diseases in which mutations are present in parental germinal cells and, therefore, in all the cells of a given organism, it is not suitable to identify sporadic diseases in which mutations might occur in specific somatic cells. This review addresses somatic DNA variations in different tissues or cells (mainly in the brain) of single individuals and discusses whether the dogma of DNA invariance between cell types is indeed correct. We will also discuss how single nucleotide somatic variations arise, focusing on the presence of specific DNA mutations in the brain., This study was supported by grants from the BBVA Foundation and MICINN-MINECO.

Unitat didàctica per a secundària (Sistema nerviós i sistema endocrí, 3er d'ESO). El·laborada dins el Màster de Formació del Professorat d'Educació Secundària Mentora: Maria Lluïsa Yebra Cueto de l'Institut Barcelona-Congrés (Barcelona) Tutor UPF: Marcel Costa Vila En aquesta unitat didàctica de 3r d’ESO estudiarem la funció de relació, duta a terme/npel sistema nerviós i el sistema endocrí, que conjuntament formen el sistema/nneuroendocrí. Per fer-ho utilitzarem com a context de la caiguda que va patir Michael/nSchumacher i que li va provocar un traumatisme cranioencefàlic. L’objectiu és que els/nalumnes coneguin la neurona (unitat funcional del sistema nerviós), les parts d’aquest/nsistema, les funcions del SN i les conseqüències d’un mal funcionament d’aquest/nsistema. Per altra banda, pretenem que els estudiants puguin identificar els components del sistema endocrí i la importància d’aquest sistema en el control i/ncoordinació de l’organisme. Hauran de saber reconèixer les principals glàndules/nendocrines, les hormones que produeixen i les seves funcions en l’organisme./nDestacarem la hipòfisi com a glàndula encarregada del control de l’activitat hormonal/nde l’organisme i el seu paper d’enllaç entre el sistema endocrí i el sistema hormonal.

Este trabajo trata de recopilar y relacionar distintos artículos médicos, con la intención de proponer un tratamiento conservador al estreñimiento. Mediante el empleo de diversas técnicas mínimamente invasivas, pretendemos ofrecer una alternativa coherente, viable y fundamentada, a los métodos clásicos que hasta ahora se han empleado en la curación de esta patología. Intentamos ver hasta dónde llegan hoy en día las investigaciones realizadas en todas las áreas de la salud sobre este tema, más allá de los estudios médicos. Y estudiar a fondo y desde muchos puntos de vista el estreñimiento primario, para así ofrecer un método de abordaje global a esta patología tan prevalente. Asimismo, incluimos algunos consejos sobre hábitos de vida saludables, ya que, aunque no somos especialistas en todos los campos de la salud, nuestra vocación como profesionales de este sector, nos obliga a llegar lo más lejos posible, en beneficio del paciente. This work aims to compile and link several medical items, with the intention to propose a conservative treatment to constipation. By employing various minimally invasive techniques, we try to provide a coherent, viable and grounded alternative to the classical methods employed until nowadays in the cure of this disease. We tried to see how far today come research in all areas of health on this subject, beyond medical studies. And thoroughly study and from many points of view the primary constipation, thus offering a method of global approach to this very prevalent disease. Also include some tips on a healthy lifestyle, because, although we are not experts in all fields of health, our vocation as professionals of health, requires us to go as far as possible, for the benefit of the patient. Grau en Fisioteràpia