Experience-dependent plasticity in early stations of sensory processing in mature brains: effects of environmental enrichment on dendrite measures in trigeminal nuclei.

Nervous systems respond with structural changes to environmental changes even in adulthood. In recent years, experience-dependent structural plasticity was shown not to be restricted to the cerebral cortex, as it also occurs at subcortical and even peripheral levels. We have previously shown that two populations of trigeminal nuclei neurons, trigeminothalamic barrelette neurons of the principal nucleus (Pr5), and intersubnuclear neurons in the caudal division of the spinal trigeminal nucleus (Sp5C) that project to Pr5 underwent morphometric and topological changes in their dendritic trees after a prolonged total or partial loss of afferent input from the vibrissae. Here we examined whether and what structural alterations could be elicited in the dendritic trees of the same cell populations in young adult rats after being exposed for 2 months to an enriched environment (EE), and how these changes evolved when animals were returned to standard housing for an additional 2 months. Neurons were retrogradely labeled with BDA delivered to, respectively, the ventral posteromedial thalamic nucleus or Pr5. Fully labeled cells were digitally reconstructed with Neurolucida and analyzed with NeuroExplorer. EE gave rise to increases in dendritic length, number of trees and branching nodes, spatial expansion of the trees, and dendritic spines, which were less pronounced in Sp5C than in Pr5 and differed between sides. In Pr5, these parameters returned, but only partially, to control values after EE withdrawal. These results underscore a ubiquity of experience-dependent changes that should not be overlooked when interpreting neuroplasticity and developing plasticity-based therapeutic strategies.post-print2959 K

Changes in the axon terminals of primary afferents from a single vibrissa in the rat trigeminal nuclei after active touch deprivation or exposure to an enriched environment.

Lasting modifications of sensory input induce structural and functional changes in the brain, but the involvement of primary sensory neurons in this plasticity has been practically ignored. Here we examine qualitatively and quantitatively the central axonal terminations of a population of trigeminal ganglion neurons whose peripheral axons innervate a single mystacial vibrissa. Vibrissa follicles are heavily innervated by myelinated and unmyelinated fibers that exit the follicle mainly through a single deep vibrissal nerve (DVN). We made intraneural injections of a mixture of cholera-toxin B (CTB) and isolectin B4, tracers for myelinated and unmyelinated fibers respectively, in three groups of young adult rats: controls, animals subjected to chronic haptic touch deprivation by unilateral whisker trimming, and rats exposed for two months to environmental enrichment. The regional and laminar pattern of terminal arborizations in the trigeminal nuclei of the brain stem did not show gross changes after sensory input modification. However, there were significant and widespread increases in the number and size of CTB-labeled varicosities in the enriched condition, and a prominent expansion in both parameters in laminae III-IV of the caudal division of the spinal nucleus in the whisker trimming condition. No obvious changes were detected in IB4-labeled terminals in laminae I-II. These results show that a prolonged exposure to changes in sensory input without any neural damage is capable of inducing structural changes in terminals of primary afferents in mature animals, and highlight the importance of peripheral structures as the presumed earliest players in sensory experience-dependent plasticity.pre-print561 K

Quantifying digital-native and legacy, national and local news websites in Spain, their topic scope and platforms

This study was supported by the Diginativemedia research projects "Digital-native media in Spain: characterization and trends", funded by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (RTI2018-093346-B-C31), and "Digital-native media in Spain: Typologies, strategies, journalistic competences and sustainability", funded by National Investigation Agency, Spanish Ministry of Science and Innovation (PID2021-122534OB-C22).Digital media have become an integral part of the journalism industry and of audience habits - in 2021 our research registered 2873 active news websites in Spain. First, this paper explores trends facing online news; it sets out the criteria used to identify a news brand as digital-native or non-native; and it presents the results of our classification. This includes: data on the presence of news titles both on proprietary platforms (print, radio, TV or app) in addition to their websites, and on external platforms (Facebook, Twitter, Instagram, YouTube and Telegram); their geographic scope (hyperlocal, local/regional or national/global); their subject (general or specialized coverage); and on ownership and language used. Almost 70% of the media were regional or local, while 60% covered general news, and one in three were linked to a print product, almost as many as those with their own app for users. Social media uptake is so widespread that more than 95% of the sites are on Facebook, with a similar number on Twitter, while more than 60% can be found on YouTube, and similarly on Instagram. Among specialized sites, sport is the largest category, comprising twice as many digital-native sites (106) than sites with traditional roots (46). The entertainment focus expands in the digital environment, and online-originated culture, business and science and technology outlets also outnumber legacy publications.Els mitjans digitals s'han convertit en una part integral de la indústria del periodisme i dels hàbits de l'audiència: el 2021, la nostra recerca va registrar 2.873 llocs web de notícies actius a Espanya. En primer lloc, aquest article explora les tendències que afronten els mitjans periodístics digitals; després, estableix els criteris utilitzats per identificar una marca de notícies com a nadiua digital o no nadiua, i finalment presenta els resultats de la nostra classificació. Això inclou: dades sobre la presència de marques periodístiques tant en plataformes pròpies (premsa, ràdio, TV, web i app), com en xarxes socials (Facebook, Twitter, Instagram, YouTube i Telegram); el seu abast geogràfic (hiperlocal, local/regional o nacional/global); la seva temàtica (cobertura general o especialitzada); la propietat i la llengua. Entre els resultats, destaca que gairebé el 70% dels mitjans eren autonòmics o locals, mentre que el 60% cobria notícies generals, i un de cada tres estava vinculat a algun producte imprès, gairebé tants com els que tenien una app pròpia per als usuaris. L'acceptació de les xarxes socials està tan estesa que més del 95% dels mitjans són a Facebook, un nombre similar són a Twitter i més del 60% es poden trobar a YouTube i a Instagram. Entre els llocs especialitzats, l'esport és la categoria més gran en els mitjans nadius digitals (106), que suposen més del doble dels mitjans no nadius especialitzats en aquesta temàtica (46). Així mateix, l'atenció a l'entreteniment s'amplia en l'entorn digital, i els mitjans nadius digitals centrats en cultura, negocis i ciència i tecnologia superen en nombre les publicacions tradicionals.Los medios digitales se han convertido en una parte integral de la industria del periodismo y de los hábitos de la audiencia: en 2021, nuestra investigación registró 2.873 sitios web de noticias activos en España. En primer lugar, este artículo explora las tendencias que afrontan los medios periodísticos digitales; después, establece los criterios utilizados para identificar una marca de noticias como nativa digital o no nativa, y finalmente presenta los resultados de nuestra clasificación. Esto incluye: datos sobre la presencia de marcas periodísticas tanto en plataformas propias (prensa, radio, TV, web y app), como en redes sociales (Facebook, Twitter, Instagram, YouTube y Telegram); su alcance geográfico (hiperlocal, local/ regional o nacional/global); su temática (cobertura general o especializada); la propiedad y la lengua. Entre los resultados, destaca que casi el 70% de los medios eran autonómicos o locales, mientras que el 60% cubría noticias generales, y uno de cada tres estaba vinculado a algún producto impreso, casi tantos como los que tenían app propia para los usuarios. La aceptación de las redes sociales está tan extendida que más del 95% de los medios están en Facebook, un número similar están en Twitter y más del 60% se pueden encontrar en YouTube y en Instagram. Entre los sitios especializados, el deporte es la categoría más grande entre los medios nativos digitales (106), que suponen más del doble de los medios no nativos especializados en esta temática (46). Asimismo, la atención al entretenimiento se amplía en el entorno digital, y los medios nativos digitales centrados en cultura, negocios y ciencia y tecnología superan en número a las publicaciones tradicionales

Journalism Expands in Spite of the Crisis: Digital-Native News Media in Spain

Digital-native news organizations have grown steadily in Spain since the mid-1990s and they have become established as a major force in the media market. Paradoxically, their biggest expansion coincided with the Great Recession (2008-2014). In fact, their numbers increased most during 2012-2013, when traditional media were cutting staff in response to the economic crisis, and unemployment rates in the media sector as a whole hit their peak. However, these digital-native news startups have yet to prove their sustainability and stability. This study uses our own database of 3,862 native and non-native digital news outlets in Spain and the Reuters Institute Digital News Report to analyze a number of characteristics of these media, such as the percentage that have gone inactive, the relative popularity of legacy brands vs. digital natives, multi-platform synergies, content subject matter, geographical location, ownership, and funding sources. Based on these quantitative parameters, this study reviews the structural strengths and weaknesses of digital-native media in the Spanish news market. Taking into account these findings, we conclude that the surge in digital-native news media observed in Spain during the Great Recession followed the pattern of creative destruction described by several economists

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain.

Background Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad. Methods Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally. Results GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases. Conclusions GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.post-print1932 K

Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain.

post-print5657 K

Sensory Input-Dependent Changes in Glutamatergic Neurotransmission- Related Genes and Proteins in the Adult Rat Trigeminal Ganglion.

Experience-dependent plasticity induces lasting changes in the structure of synapses, dendrites, and axons at both molecular and anatomical levels. Whilst relatively well studied in the cortex, little is known about the molecular changes underlying experience-dependent plasticity at peripheral levels of the sensory pathways. Given the importance of glutamatergic neurotransmission in the somatosensory system and its involvement in plasticity, in the present study, we investigated gene and protein expression of glutamate receptor subunits and associated molecules in the trigeminal ganglion (TG) of young adult rats. Microarray analysis of naïve rat TG revealed significant differences in the expression of genes, coding for various glutamate receptor subunits and proteins involved in clustering and stabilization of AMPA receptors, between left and right ganglion. Long-term exposure to sensory-enriched environment increased this left–right asymmetry in gene expression. Conversely, unilateral whisker trimming on the right side almost eliminated the mentioned asymmetries. The above manipulations also induced side-specific changes in the protein levels of glutamate receptor subunits. Our results show that sustained changes in sensory input induce modifications in glutamatergic transmission-related gene expression in the TG, thus supporting a role for this early sensory-processing node in experience-dependent plasticity.post-print804 K

Multiple Morphometric Assessment of Microglial Cells in Deafferented Spinal Trigeminal Nucleus.

Microglia (MG) are the first cells to react to the abnormal incoming signals that follow an injury of sensory nerves and play a critical role in the development and maintenance of neuropathic pain, a common sequel of nerve injuries. Here we present population data on cell number, soma size, and length of processes of MG in the caudal division of the spinal trigeminal nucleus (Sp5C) in control mice and at the peak of microgliosis (7 days) following unilateral transection of the infraorbital nerve (IoN). The study is performed combining several bias- and assumption-free imaging and stereological approaches with different immunolabeling procedures, with the objective of tackling some hard problems that often hinder proper execution of MG morphometric studies. Our approach may easily be applied to low-density MG populations, but also works, with limited biases, in territories where MG cell bodies and processes form dense meshworks. In controls, and contralaterally to the deafferented side, MG cell body size and shape and branching pattern matched well the descriptions of “resting” or “surveillant” MG described elsewhere, with only moderate intersubject variability. On the superficial laminae of the deafferented side, however, MG displayed on average larger somata and remarkable diversity in shape. The number of cells and the length of MG processes per mm3 increased 5 and 2.5 times, respectively, indicating a net 50% decrease in the mean length of processes per cell. By using specific immunolabeling and cell sorting of vascular macrophages, we found only a negligible fraction of these cells in Sp5C, with no differences between controls and deafferented animals, suggesting that blood-borne monocytes play at most a very limited role in the microgliosis occurring following sensory nerve deafferentation. In sum, here we present reliable morphometric data on MG in control and deafferented trigeminal nuclei using efficient methods that we propose may equally be applied to any morphometric population analysis of these cells under different physiological or pathological conditions.post-print1841 K

Quantifying digital-native and legacy, national and local news websites in Spain, their topic scope and platforms

Digital media have become an integral part of the journalism industry and of audience habits – in 2021 our research registered 2873 active news websites in Spain. First, this paper explores trends facing online news; it sets out the criteria used to identify a news brand as digital-native or non-native; and it presents the results of our classification. This includes: data on the presence of news titles both on proprietary platforms (print, radio, TV or app) in addition to their websites, and on external platforms (Facebook, Twitter, Instagram, YouTube and Telegram); their geographic scope (hyperlocal, local/regional or national/global); their subject (general or specialized coverage); and on ownership and language used. Almost 70% of the media were regional or local, while 60% covered general news, and one in three were linked to a print product, almost as many as those with their own app for users. Social media uptake is so widespread that more than 95% of the sites are on Facebook, with a similar number on Twitter, while more than 60% can be found on YouTube, and similarly on Instagram. Among specialized sites, sport is the largest category, comprising twice as many digital-native sites (106) than sites with traditional roots (46). The entertainment focus expands in the digital environment, and online-originated culture, business and science and technology outlets also outnumber legacy publications

Chronic administration of P2X7 receptor antagonist JNJ-47965567 delays disease onset and progression, and improves motor performance in ALS SOD1 (G93A) female mice

Neuroinflammation is one of the main physiopathological mechanisms of amyotrophic lateral sclerosis (ALS), produced by the chronic activation of microglia in the CNS. This process is triggered by the persistent activation of the ATP-gated P2X7 receptor (P2RX7, hereafter referred to as P2X7R). The present study aimed to evaluate the effects of the chronic treatment with the P2X7R antagonist JNJ-47965567 in the development and progression of ALS in the SOD1 murine model. SOD1 mice were intraperitoneally (i.p.) injected with either 30 mg/kg of JNJ-47965567 or vehicle 4 times per week, from pre-onset age (here, postnatal day 60; P60) until study endpoint. Body weight, motor coordination, phenotypic score, disease onset and survival were measured throughout the study, and compared between vehicle- and drug-injected groups. Treatment with the P2X7R antagonist JNJ-47965567 delayed disease onset, reduced body weight loss and improved motor coordination and phenotypic score in female SOD1 mice, although it did not increase lifespan. Interestingly, neither beneficial nor detrimental effects were observed in males in any of the analyzed parameters. Treatment did not affect motor neuron survival or ChAT, Iba-1 and P2X7R protein expression in endpoint individuals of mixed sexes. Overall, chronic administration of JNJ-47965567 for 4 times per week to SOD1 mice from pre-onset stage altered disease progression in female individuals while it did not have any effect in males. Our results suggest a partial, yet important, effect of P2X7R in the development and progression of ALS. G93A G93A G93A G93AThis project was supported by the European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 766124; the Spanish Ministry of Science, Technology and Innovation (SAF2016-78892R); and Fundación Teófilo Hernando