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Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomaticR6/1HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in theR6/1HD mouse model.SIGNIFICANCE STATEMENTUnderstanding brain circuit alterations in brain disorders is critical for developing circuit-based therapeutic interventions. The cortico-striatal circuit is the most prominently disturbed in Huntington's disease (HD); and particularly, M2 cortex has a prominent role. However, the same M2 cortical neurons send additional projections to several brain regions beyond striatum. We characterized new structural and functional circuitry alterations of M2 cortex in HD mouse models and found that M2 cortex projection to the superior colliculus (SC) was deeply impaired. Moreover, we describe differential responses to unexpected sensory stimulus in HD mouse models, which relies on SC function. Our data highlight the involvement of M2 cortex in SC-dependent sensory processing and its alterations in HD pathophysiology.

The consequences of extremely intense long-term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose-response relationship, and mechanisms in a rat model of endurance training. Five-week-old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sedentary (SED) group for 16 weeks. MOD rats showed the highest motivation and learning capacity in operant conditioning experiments; SED and INT presented similar results. In vivo MRI demonstrated enhanced global and regional connectivity efficiency and clustering as well as a higher cerebral blood flow (CBF) in MOD but not INT rats compared with SED. In the cortex, downregulation of oxidative phosphorylation complex IV and AMPK activation denoted mitochondrial dysfunction in INT rats. An imbalance in cortical antioxidant capacity was found between MOD and INT rats. The MOD group showed the lowest hippocampal brain-derived neurotrophic factor levels. The mRNA and protein levels of inflammatory markers were similar in all groups. In conclusion, strenuous long-term exercise yields a lesser improvement in learning ability than moderate exercise. Blunting of MOD-induced improvements in CBF and connectivity efficiency, accompanied by impaired mitochondrial energetics and, possibly, transient local oxidative stress, may underlie the findings in intensively trained rats.

© The Author(s) 2021., Ketamine has rapid and robust antidepressant effects. However, unwanted psychotomimetic effects limit its widespread use. Hence, several studies examined whether GluN2B-subunit selective NMDA antagonists would exhibit a better therapeutic profile. Although preclinical work has revealed some of the mechanisms of action of ketamine at cellular and molecular levels, the impact on brain circuitry is poorly understood. Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine and Ro 25-6981 (a GluN2B-subunit selective antagonist), but the changes in the microstructure of gray and white matter have received less attention. Here, the effects of ketamine and Ro 25-6981 on gray and white matter integrity in male Sprague–Dawley rats were determined using diffusion-weighted magnetic resonance imaging (DWI). In addition, DWI-based structural brain networks were estimated and connectivity metrics were computed at the regional level. Immunohistochemical analyses were also performed to determine whether changes in myelin basic protein (MBP) and neurofilament heavy-chain protein (NF200) may underlie connectivity changes. In general, ketamine and Ro 25-6981 showed some opposite structural alterations, but both compounds coincided only in increasing the fractional anisotropy in infralimbic prefrontal cortex and dorsal raphe nucleus. These changes were associated with increments of NF200 in deep layers of the infralimbic cortex (together with increased MBP) and the dorsal raphe nucleus. Our results suggest that the synthesis of NF200 and MBP may contribute to the formation of new dendritic spines and myelination, respectively. We also suggest that the increase of fractional anisotropy of the infralimbic and dorsal raphe nucleus areas could represent a biomarker of a rapid antidepressant response., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación (PI13/00038, PI16/00217 and PI19/00170 to A.A.) that were co-funded by the European Regional Development Fund (‘A way to build Europe’); Generalitat Valenciana, Conselleria d’ Educació, Investigació, Cultura i Esport (GV/2018/049 to A.B-S.); Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00 to F.P.-C.). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine β-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

BackgroundBrain electrical stimulation techniques take advantage of the intrinsic plasticity of the nervous system, opening a wide range of therapeutic applications. Vagus nerve stimulation (VNS) is an approved adjuvant for drug-resistant epilepsy and depression. Its non-invasive form, auricular transcutaneous VNS (atVNS), is under investigation for applications, including cognitive improvement.ObjectiveWe aimed to study the effects of atVNS on brain connectivity, under conditions that improved memory persistence in CD-1 male mice.MethodsAcute atVNS in the cymba conchae of the left ear was performed using a standard stimulation protocol under light isoflurane anesthesia, immediately or 3 h after the training/familiarization phase of the novel object-recognition memory test (NORT). Another cohort of mice was used for bilateral c-Fos analysis after atVNS administration. Spearman correlation of c-Fos density between each pair of the thirty brain regions analyzed allowed obtaining the network of significant functional connections in stimulated and non-stimulated control brains.ResultsNORT performance was enhanced when atVNS was delivered just after, but not 3 h after, the familiarization phase of the task. No alterations in c-Fos density were associated to electrostimulation, but a significant effect of atVNS was observed on c-Fos-based functional connectivity. atVNS induced a clear reorganization of the network, increasing the inter-hemisphere connections and the connectivity of locus coeruleus.ConclusionOur results provide new insights in the effects of atVNS on memory performance and brain connectivity extending our knowledge of the biological mechanisms of bioelectronics in medicine.HighlightsatVNS, delivered immediately after NORT training phase, improves memory persistenceatVNS did not promote significant changes in brain c-Fos densityatVNS induced a significant reorganization of c-Fos-based functional brain networkatVNS produced an enhancement in correlated activity between hemispheresatVNS did not engage the prefrontal-retrosplenial axis, characteristic of the DMN

The premotor cortical area -M2 cortex in rodents- connection to the striatum is involved in movement and prominently affected in Huntington’s Disease (HD). M2 cortex also projects to the superior colliculus (SC), implicated in oculomotor functions (i.e. saccades) and visual perception. Here, we investigated the contribution of M2 cortex – SC circuit to HD physiopathology in male mice. Using fMRI, we observed that M2 cortex functional connectivity with the SC was the most prominently affected circuit in the symptomatic R6/1 HD mouse model. Structural alterations were also detected by tractography and viral tracing. HD mice showed decreased defensive behavioral responses towards an unexpected visual stimuli, such as a moving robo-beetle, and decreased locomotion upon unexpected flash of light. Additionally, optogenetic M2 cortex – SC stimulation promoted avoidance responses towards the robo-beetle in WT, but not HD mice. Though, DWI measurements in vivo and ex vivo electrophysiological responses to optogenetic and electrical stimuli in the SC suggested preserved brain structure. Finally, GCamp6f fluorescence recordings with fiber photometry indicated that aberrant M2 cortex engagement might be the underlying mechanism of visual perception alterations in HD. Collectively, our findings point to a key role of M2 cortex - SC circuit alterations in HD pathophysiology.

Preparation for motherhood requires a myriad of physiological and behavioural adjustments throughout gestation to provide an adequate environment for proper embryonic development. Cravings for highly palatable foods are highly prevalent during pregnancy and contribute to the maintenance and development of gestational overweight or obesity. However, the neurobiology underlying the distinct ingestive behaviours that result from craving specific foods remain unknown. Here we show that mice, similarly to humans, experience gestational food craving-like episodes. These episodes are associated with a brain connectivity reorganization that affects key components of the dopaminergic mesolimbic circuitry, which drives motivated appetitive behaviours and facilitates the perception of rewarding stimuli. Pregnancy engages a dynamic modulation of dopaminergic signalling through neurons expressing dopamine D2 receptors in the nucleus accumbens, which directly modulate food craving-like events. Importantly, persistent maternal food craving-like behaviour has long-lasting effects on the offspring, particularly in males, leading to glucose intolerance, increased body weight and increased susceptibility to develop eating disorders and anxiety-like behaviours during adulthood. Our results reveal the cognitively motivated nature of pregnancy food cravings and advocates for moderating emotional eating during gestation to prevent deterioration of the offspring’s neuropsychological and metabolic health., This study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725004) and supported by: ‘la Caixa’ Foundation (ID100010434) under agreement LCF/PR/HR19/52160016 and the CERCA Programme/Generalitat de Catalunya (to M.C.); grant no. PID2019-105136RB-100, Spanish Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (ERDF; to A.B.); Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF) NEUROPREG (grant agreement no. 891247; to R.H-T.); the Spanish Ministry of Science and Innovation, Juan de la Cierva fellowship (IJC2018-037341-I to S.R.); Miguel Servet contract (CP19/00083) from Instituto de Salud Carlos III co-financed by ERDF (to A.O.). This work was carried out in part at the Esther Koplowitz Centre.

Peripheral inputs to the brain continuously shape its function and can influence the formation of non-emotional memory, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptors (CB1R), widely distributed in the organism, is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing non-emotional memory in mice, we have now found a relevant role of peripheral CB1R in the formation of persistent memory. Indeed, peripherally restricted CB1R antagonism by using AM6545 showed a mnemonic effect that was occluded in adrenalectomized mice, after peripheral adrenergic blockade, or when vagus nerve was chemogenetically inhibited. Genetic CB1R deletion in dopamine β-hydroxylase-expressing cells enhanced the formation of persistent memory, supporting a role of peripheral CB1R modulating the adrenergic tone. Notably, brain connectivity was affected by peripheral CB1R inhibition, and locus coeruleus activity and extracellular hippocampal norepinephrine, were increased. In agreement, intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects. Together, we disclose a novel peripheral mechanism relevant for the modulation of the formation of persistent non-emotional memory.

Este artículo estudia la trayectoria biográfica y artística de Concepción Rodríguez, entre 1800 y 1836. Fue la actriz española más relevante de las primeras décadas del siglo XIX y el modelo en el que se inspiró su sucesora: Matilde Díez. Nos ocupamos de aquellos aspectos por los que fue considerada una gran dama de la escena. En primer lugar, su repertorio, basado, entre otros autores, en las obras de Bretón de los Herreros. En segundo lugar, la recepción crítica, que destacó su sensibilidad, su naturalidad y sus cualidades vocales. En tercer lugar, en los tratados de declamación que recogen como ejemplo su interpretación de Dido, fundadora de Cartago. Por último, en su aceptación social, que se advierte en las composiciones poéticas laudatorias que se le dedican y también en su nombramiento como Maestra honoraria de la Escuela de Declamación Española., This paper focuses on Concepción Rodríguez’s personal and artistic trajectory, between 1800 and 1836. She was one of the greatest Spanish actresses in the first few decades of the 19th century and she became a model and a source of inspiration for her successor: Matilde Díez. We analyse those issues for which she was considered a great actress of the scene. Firstly, we study her drama repertoire that was based, among others, on Bretón de los Herreros’ plays. Secondly, we consider the theatre reviews of her performances. These reviews highlight her sensitivity, naturalness and vocal skills. Thirdly, we focus on the treatises on acting that take her performance in Dido, fundadora de Cartago as a model example. Finally, it is considered her status in the society that improves through the poems admirers write for her and thanks to her appointment as Honorary teacher of the School of Spanish Drama.

DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15 zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structures during development. DHX15 mice depicted lower vascular density and impaired lymphatic function postnatally. RNAseq and proteome analysis of DHX15 silenced endothelial cells revealed differential expression of genes involved in the metabolism of ATP biosynthesis. The validation of these results demonstrated a lower activity of the Complex I in the mitochondrial membrane of endothelial cells, resulting in lower intracellular ATP production and lower oxygen consumption. After injection of syngeneic LLC1 tumor cells, DHX15 mice showed partially inhibited primary tumor growth and reduced lung metastasis. Our results revealed an important role of DHX15 in vascular physiology and pave a new way to explore its potential use as a therapeutical target for metastasis treatment., This study was supported by grants from MCIN/AEI/10.13039/501100011033 (SAF2016-75358-R and PDI2019-105502RB-100 to MM-R, SAF2017-85877R, PID2019-111669RB-100, PID2020-115055RB-I00). CIBERehd, CIBERonc and CIBERbbn are financed by the Instituto de Salud Carlos III. I.P. was recipient of a predoctoral fellowship supported by MCIN/AEI/10.13039/501100011033 y FSE “El FSE invierte en tu futuro” (BES-2017-080823). A.E-.C. is funded by ISCIII of the MINECO (reference PT17/0009/0019) and co-financed by FEDER. J.R-.V. was a recipient of a BIOTRACK Postdoctoral Fellowship supported by the European Community’s Seventh Framework Programme and the MINECO (Contract 229673). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. The center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208, and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595). The authors would like to thank Drs. Simone Calzolari, Rafael Miñana and Javier Terriente from ZeClinics for their helpful collaboration with the zebrafish model generation and experimentation.

Introduction: A U-shaped relationship between exercise load and cardiovascular risk has been demonstrated. In the brain, moderate exercise improves cognitive performance but the consequences of intense exercise remain unknown. We aimed to describe the effects of moderate and intensive exercise load on brain structure and function. Methods: Male Wistar rats were subjected to moderate (MOD, 35 cm/s for 45 min, n=8) or intense (INT, 60 cm/s for 60 min, n=8) exercise for 16 weeks, 5 days/week; sedentary rats (SED, n=10) were used as controls. At 16 weeks, learning and motivation tests, and brain magnetic resonance (MR) were obtained. In MR, structural brain networks were analyzed using fractional anisotropy normalized connectomes, and cerebral blood flow (CBF) was assessed using pulsed arterial spin labelling. BDNF levels were analysed in plasma, hippocampus and frontal cortex samples with ELISA. Results: MOD rats showed a greater motivation than SED rats and enhanced learning capacity than INT rats. In the MR, only moderate exercise increased global and local efficiency and average clustering coefficient. Global CBF was increased by moderate but not intensive exercise (Fig A). CBF was subsequently assessed at specific brain regions. In comparison to SED, MOD rats presented a higher CBF in the right and left cortex, and in the left hippocampus; in INT rats, CBF was higher only in the left cortex compared to SED (Fig B). MOD training induced a significant decrease in BDNF protein levels in the hippocampus compared to both SED and INT groups. No significant differences were found on BDNF levels in plasma and frontal cortex samples among groups. Conclusions: In a rat model, moderate exercise induces brain structural and functional improvements that are not perpetuated with intensive exercise, supporting the existence of a U-shaped relationship between exercise load and brain function.

DHX15 is an ATP-dependent RNA helicase involved in pre-mRNA splicing and a downstream substrate for Akt1, which plays a significant role in vascular biology. The aim of this study was to explore the regulatory function of DHX15 over the vasculature and endothelial cell biology. Results: DHX15-/- was lethal in mouse and zebrafish embryos. DHX15-/- zebrafish also showed an undeveloped parachordal line, which leads to the formation of lymphatic structures. DHX15+/- mice triggered lower vascular network density and impaired lymphatic function postnatally. Transcriptome and proteome analysis of DHX15 silenced LEC revealed alterations in the glycolysis and gluconeogenesis pathways. The validation of these results demonstrated an uncoupling of the glycolysis with the oxidation of pyruvate in the mitochondria and a lower activity of the Complex I, resulting in lower cellular ATP production. Noteworthy, DHX15+/- mice partially inhibited primary tumor growth and reduced lung metastasis after injection of LLC1 tumor cells.

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most pathological features were successfully reverted, we observed a high degree of metabolic dysfunction irreversibility in visceral white adipose tissue, characterised by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and apparent global phenotypic recovery, obesity specifically triggered in visceral adipose a cascade of events progressing from mitochondrial metabolic and proteostatic defects to widespread cellular stress, which compromises its biosynthetic and recycling capacity. Our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in white adipose tissue, becoming a significant milestone in disease progression.

Huntington's disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of the basal ganglia. The cerebral cortex is the main striatal afferent, and progressive cortico-striatal disconnection characterizes HD. We mapped striatal network dysfunction in HD mice to ultimately modulate the activity of a specific cortico-striatal circuit to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo indicates cortico-striatal and thalamo-striatal functional network deficits and reduced glutamate/glutamine ratio in the striatum of HD mice. Moreover, optogenetically-induced glutamate release from M2 cortex terminals in the dorsolateral striatum (DLS) was undetectable in HD mice and striatal neurons show blunted electrophysiological responses. Remarkably, repeated M2-DLS optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that selective stimulation of the M2-DLS pathway can become an effective therapeutic strategy in HD., We are very grateful to Ana Lopez (María de Maeztu Unit of Excellence, Institute of Neurosciences, University of Barcelona, MDM-2017–0729, Ministry of Science, Innovation, and Universities) and Maite Muñoz for their excellent technical support. This work has been funded by the Spanish Ministry of Sciences, Innovation and Universities through projects no. SAF2017-88076-R, RETICS de Terapia Celular, Instituto de Salud Carlos III (RD06/0010/0006), and la Marato´ de TV3. This research is part of NEUROPA. The NEUROPA Project has received funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 863214.

Uno de los objetivos del teatro durante la Ilustración fue mejorar la declamación actoral. Su ejercicio, considerado como un arte liberal, se codificó en reglas objetivas difundidas en distintos tratados. Muchos de ellos, escritos por actores, revelan una dependencia de saberes ya consolidados o de otras artes miméticas, como la retórica clásica y la pintura. Los textos incorporaban el estudio de las pasiones, para responder al nuevo drama burgués. El proceso por el que el actor alcanzaba la expresividad emocional está presente en la paradoja diderotiana, y en otros textos publicados y traducidos en el XVIII: "Le comédien", de Rémond de Saint-Albine; "L'art du théâtre", de F. Riccoboni; "An Essay on the Art of Acting", de A. Hill; "Desengaño de los engaños", de Rezano Imperial; "Ideen zu Einer Mimik", de J. J. Engel, etc. Estos ejemplos, como estudiamos en este artículo, confirman las relaciones entre las distintas escenas europeas, en las que predomina el referente francés. One of the aims in the Enlightenment period stage was to improve player’s delivery. This practice, regarded as a liberal art, was developed into objective rules that were compiled in several treatises on acting. Many of them, written by actors, reveal their dependence on consolidated knowledges or others mimetic arts, like classical rhetoric or painting. Treatises include how to express the passions properly to suit with the new genre: the drame burgeois. The means by which players get emotional expression appear in The Paradox of Acting among others published or translated books through the 18th century: Le comédien, by Rémond de Saint-Albine; L’art du théâtre, by F. Riccoboni; An Essay on the Art of Acting, by A. Hill; Desengaño de los engaños, by A. Rezano Imperial; or Ideen zu Einer Mimik, by J. J. Engel. These examples, as we can verify in this paper, confirm the European stage interrelationships and the predominance of the French paradigm. Este trabajo ha sido realizado en el marco de la beca José Castillejo (referencia CAS2015/0199) para estancias de movilidad de profesores e investigadores en centros extranjeros de enseñanza superior e investigación financiada por el MECD. Grupo receptor CREC. Paris 3.

Este artículo se ocupa de las clases de Declamación reabiertas en la Escuela Nacional de Música en 1874. Para impartirlas se nombró por primera vez a mujeres. El gobierno escogió a las mejores actrices de la escena: Matilde Díez y Teodora Lamadrid. Analizamos las dificultades que sortearon para desempeñar sus clases, las obras que ensayaban y el tratado de declamación que seguían las alumnas para desarrollar sus cualidades. Este tratado insistía en el realismo escénico y la perfección vocal. Estudiamos también cómo esta formación, una de las pocas opciones para las mujeres del XIX, mejoró la imagen pública de estas maestras. This paper focuses on the reopened Drama Studies at the National School of Music in 1874. For the first time, women were appointed teachers of Acting. The Government chose the best stage actresses of the time: Matilde Díez and Teodora Lamadrid. We will consider the difficulties they had to overcome to teach their lessons, the plays they rehearsed and the treatise on acting with which the disciples developed their skills. This treatise meant for the scenic realism and was especially attentive to the voice. We will also study how these lessons, one of the few training options for women in the XIX century, improved the public imagen of these teachers. Artículo realizado en el marco del proyecto de investigación HAR2011-27540 financiado por el MINECO.

The research of Alzheimer’s disease (AD) in its early stages and its progression till symptomatic onset is essential to understand the pathology and investigate new treatments. Animal models provide a helpful approach to this research, since they allow for controlled follow-up during the disease evolution. In this work, transgenic TgF344-AD rats were longitudinally evaluated starting at 6 months of age. Every 3 months, cognitive abilities were assessed by a memory-related task and magnetic resonance imaging (MRI) was acquired. Structural and functional brain networks were estimated and characterized by graph metrics to identify differences between the groups in connectivity, its evolution with age, and its influence on cognition. Structural networks of transgenic animals were altered since the earliest stage. Likewise, aging significantly affected network metrics in TgF344-AD, but not in the control group. In addition, while the structural brain network influenced cognitive outcome in transgenic animals, functional network impacted how control subjects performed. TgF344-AD brain network alterations were present from very early stages, difficult to identify in clinical research. Likewise, the characterization of aging in these animals, involving structural network reorganization and its effects on cognition, opens a window to evaluate new treatments for the disease., Author Summary We have applied magnetic resonance image–based connectomics to characterize TgF344-AD rats, a transgenic model of Alzheimer’s disease (AD). This represents a highly translational approach, what is essential to investigate potential treatments. TgF344-AD animals were evaluated from early to advanced ages to describe alterations in brain connectivity and how brain networks are affected by age. Results showed that aging had a bigger impact in the structural connectivity of the TgF344-AD than in control animals, and that changes in the structural network, already observed at early ages, significantly influenced cognitive outcome of transgenic animals. Alterations in connectivity were similar to that described in AD human studies and complement them by providing insights into earlier stages and a plot of AD effects throughout the whole life span.

Background Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions. Objective In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system. Methods Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI. Results The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection. Conclusion Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.