RESUMEN

LAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is a devastating congenital muscular dystrophy that is caused by mutations in the LAMA2 gene encoding laminin-α2, the long chain of several heterotrimeric laminins. Laminins are essential components of the extracellular matrix that interface with underlying cells. The pathology of LAMA2 MD patients is dominated by an early-onset, severe muscular dystrophy that ultimately leads to death by respiratory insufficiency. However, pathology in nonmuscle tissues has been described. Prior work in the dyW /dyW mouse model for LAMA2 MD has shown that two linker proteins, mini-agrin and αLNNd, when expressed in skeletal muscle fibers, greatly increase survival from a few months up to more than 2 years. However, the restoration of skeletal muscle function accentuates the pathology in nonmuscle tissue in dyW /dyW mice, first and foremost in the peripheral nerve resulting in paralysis of the hind limbs. We now show that the expression of the two linker proteins in all tissues ameliorates the muscular dystrophy and prevents the appearance of the hind limb paralysis. Importantly, the same ameliorating effect of the linker proteins was seen in dy3K /dy3K mice, which represent the most severe mouse model of LAMA2 MD. In summary, these data show that the two linker proteins can compensate the loss of laminin-α2 in muscle and peripheral nerve, which are the two organs most affected in LAMA2 MD. These results are of key importance for designing appropriate expression constructs for mini-agrin and αLNNd to develop a gene therapy for LAMA2 MD patients.

RESUMEN

With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.

Asunto(s)

Envejecimiento/fisiología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Fibras Musculares Esqueléticas/patología , Unión Neuromuscular/patología , Sarcopenia/patología , Envejecimiento/efectos de los fármacos , Animales , Línea Celular , Modelos Animales de Enfermedad , Electromiografía , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Humanos , Captura por Microdisección con Láser , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Ratones , Mioblastos , Unión Neuromuscular/efectos de los fármacos , Técnicas de Placa-Clamp , RNA-Seq , Sarcopenia/genética , Sarcopenia/fisiopatología , Sarcopenia/prevención & control , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Sirolimus/administración & dosificación

RESUMEN

BACKGROUND: The mammalian target of rapamycin complex 2 (mTORC2), containing the essential protein rictor, regulates cellular metabolism and cytoskeletal organization by phosphorylating protein kinases, such as PKB/Akt, PKC, and SGK. Inactivation of mTORC2 signaling in adult skeletal muscle affects its metabolism, but not muscle morphology and function. However, the role of mTORC2 in adult muscle stem cells (MuSCs) has not been investigated. METHOD: Using histological, biochemical, and molecular biological methods, we characterized the muscle phenotype of mice depleted for rictor in the Myf5-lineage (RImyfKO) and of mice depleted for rictor in skeletal muscle fibers (RImKO). The proliferative and myogenic potential of MuSCs was analyzed upon cardiotoxin-induced injury in vivo and in isolated myofibers in vitro. RESULTS: Skeletal muscle of young and 14-month-old RImyfKO mice appeared normal in composition and function. MuSCs from young RImyfKO mice exhibited a similar capacity to proliferate, differentiate, and fuse as controls. In contrast, the number of MuSCs was lower in young RImyfKO mice than in controls after two consecutive rounds of cardiotoxin-induced muscle regeneration. Similarly, the number of MuSCs in RImyfKO mice decreased with age, which correlated with a decline in the regenerative capacity of mutant muscle. Interestingly, reduction in the number of MuSCs was also observed in 14-month-old RImKO muscle. CONCLUSIONS: Our study shows that mTORC2 signaling is dispensable for myofiber formation, but contributes to the homeostasis of MuSCs. Loss of mTORC2 does not affect their myogenic function, but impairs the replenishment of MuSCs after repeated injuries and their maintenance during aging. These results point to an important role of mTORC2 signaling in MuSC for muscle homeostasis.

Asunto(s)

Autorrenovación de las Células , Mioblastos/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/metabolismo , Animales , Células Cultivadas , Femenino , Masculino , Ratones , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiología , Mioblastos/citología , Mioblastos/fisiología , Factor 5 Regulador Miogénico/genética , Factor 5 Regulador Miogénico/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/genética , Transducción de Señal

RESUMEN

The formation of multi-nucleated muscle fibers from progenitors requires the fine-tuned and coordinated regulation of proliferation, differentiation and fusion, both during development and after injury in the adult. Although some of the key factors that are involved in the different steps are well known, how intracellular signals are coordinated and integrated is largely unknown. Here, we investigated the role of the cell-growth regulator mTOR by eliminating essential components of the mTOR complexes 1 (mTORC1) and 2 (mTORC2) in mouse muscle progenitors. We show that inactivation of mTORC1, but not mTORC2, in developing muscle causes perinatal death. In the adult, mTORC1 deficiency in muscle stem cells greatly impinges on injury-induced muscle regeneration. These phenotypes are because of defects in the proliferation and fusion capacity of the targeted muscle progenitors. However, mTORC1-deficient muscle progenitors partially retain their myogenic function. Hence, our results show that mTORC1 and not mTORC2 is an important regulator of embryonic and adult myogenesis, and they point to alternative pathways that partially compensate for the loss of mTORC1.This article has an associated 'The people behind the papers' interview.

Asunto(s)

Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Células Cultivadas , Immunoblotting , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 2 de la Rapamicina/genética , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Ratones , Ratones Noqueados , Desarrollo de Músculos/genética , Desarrollo de Músculos/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina-Treonina Quinasas TOR/genética

RESUMEN

Honeybees maintain their colony throughout the cold winters, a strategy that enables them to make the most of early spring flowers. During this period, their activity is mostly limited to thermoregulation, while foraging and brood rearing are stopped. Less is known about seasonal changes to the essential task of defending the colony against intruders, which is regulated by the sting alarm pheromone. We studied the stinging responsiveness of winter bees exposed to this scent or a control (solvent). Surprisingly, winter bees, while maintaining their responsiveness in control conditions, did not increase stinging frequency in response to the alarm pheromone. This was not owing to the bees not perceiving the pheromone, as shown by calcium imaging of the antennal lobes. As the alarm pheromone is thought to act through an increase in brain serotonin levels, ultimately causing heightened defensiveness, we checked if serotonin treatments would affect the stinging behaviour of winter bees. Indeed, treated winter bees became more inclined to sting. Thus, we postulate that loss of responsiveness to the sting alarm pheromone is based on a partial or total disruption of the mechanism converting alarm pheromone perception into high serotonin levels in winter bees.

Asunto(s)

Abejas/efectos de los fármacos , Feromonas/metabolismo , Estaciones del Año , Serotonina/metabolismo , Animales , Abejas/fisiología , Conducta Animal , Calcio/metabolismo , Mordeduras y Picaduras de Insectos , Bulbo Olfatorio/metabolismo , Conducta Social

RESUMEN

The defence of a society often requires that some specialized members coordinate to repel a threat at personal risk. This is especially true for honey bee guards, which defend the hive and may sacrifice their lives upon stinging. Central to this cooperative defensive response is the sting alarm pheromone, which has isoamyl acetate (IAA) as its main component. Although this defensive behaviour has been well described, the neural mechanisms triggered by IAA to coordinate stinging have long remained unknown. Here we show that IAA upregulates brain levels of serotonin and dopamine, thereby increasing the likelihood of an individual bee to attack and sting. Pharmacological enhancement of the levels of both amines induces higher defensive responsiveness, while decreasing them via antagonists decreases stinging. Our results thus uncover the neural mechanism by which an alarm pheromone recruits individuals to attack and repel a threat, and suggest that the alarm pheromone of honey bees acts on their response threshold rather than as a direct trigger.

Asunto(s)

Abejas/fisiología , Aminas Biogénicas/metabolismo , Pentanoles/metabolismo , Feromonas/metabolismo , Animales , Encéfalo/metabolismo , Mecanismos de Defensa , Conducta Social

RESUMEN

Laminins are large heterotrimers composed of the α, ß and γ subunits with distinct tissue-specific and developmentally regulated expression patterns. The laminin-α2 subunit, encoded by the LAMA2 gene, is expressed in skeletal muscle, Schwann cells of the peripheral nerve and astrocytes and pericytes of the capillaries in the brain. Mutations in LAMA2 cause the most common type of congenital muscular dystrophies, called LAMA2 MD or MDC1A. The disorder manifests mostly as a muscular dystrophy but slowing of nerve conduction contributes to the disease. There are severe, non-ambulatory or milder, ambulatory variants, the latter resulting from reduced laminin-α2 expression and/or deficient laminin-α2 function. Lm-211 (α2ß1γ1) is responsible for initiating basement membrane assembly. This is primarily accomplished by anchorage of Lm-211 to dystroglycan and α7ß1 integrin receptors, polymerization, and binding to nidogen and other structural components. In LAMA2 MD, Lm-411 replaces Lm-211; however, Lm-411 lacks the ability to polymerize and bind to receptors. This results in a weakened basement membrane leading to the disease. The possibility of introducing structural repair proteins that correct the underlying abnormality is an attractive therapeutic goal. Recent studies in mouse models for LAMA2 MD reveal that introduction of laminin-binding linker proteins that restore lost functional activities can substantially ameliorate the disease. This review discusses the underlying mechanism of this repair and compares this approach to other developing therapies employing pharmacological treatments.

Asunto(s)

Laminina/química , Laminina/deficiencia , Distrofias Musculares/genética , Animales , Membrana Basal/química , Membrana Basal/metabolismo , Distroglicanos/metabolismo , Humanos , Integrinas/metabolismo , Laminina/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Distrofias Musculares/metabolismo , Mutación , Unión Proteica

RESUMEN

LAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is the most frequent form of early-onset, fatal congenital muscular dystrophies. It is caused by mutations in LAMA2, the gene encoding laminin-α2, the long arm of the heterotrimeric (α2, ß1, and γ1) basement membrane protein laminin-211 (Lm-211). We establish that despite compensatory expression of laminin-α4, giving rise to Lm-411 (α4, ß1, and γ1), muscle basement membrane is labile in LAMA2 MD biopsies. Consistent with this deficit, recombinant Lm-411 polymerized and bound to cultured myotubes only weakly. Polymerization and cell binding of Lm-411 were enhanced by addition of two specifically designed linker proteins. One, called αLNNd, consists of the N-terminal part of laminin-α1 and the laminin-binding site of nidogen-1. The second, called mini-agrin (mag), contains binding sites for laminins and α-dystroglycan. Transgenic expression of mag and αLNNd in a mouse model for LAMA2 MD fully restored basement membrane stability, recovered muscle force and size, increased overall body weight, and extended life span more than five times to a maximum survival beyond 2 years. These findings provide a mechanistic understanding of LAMA2 MD and establish a strong basis for a potential treatment.

Asunto(s)

Membrana Basal/metabolismo , Laminina/metabolismo , Distrofia Muscular Animal/metabolismo , Proteínas Recombinantes/metabolismo , Adolescente , Animales , Membrana Basal/patología , Peso Corporal , Niño , Preescolar , Humanos , Ratones Transgénicos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Distrofias Musculares/metabolismo , Distrofias Musculares/patología , Distrofia Muscular Animal/patología , Transgenes

RESUMEN

Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation in Lama2 (dy2J mice) express a nonpolymerizing form of laminin-211 (Lm211) and are a model for ambulatory-type Lmα2-deficient muscular dystrophy. Here, we developed transgenic dy2J mice with muscle-specific expression of αLNNd, a laminin/nidogen chimeric protein that provides a missing polymerization domain. Muscle-specific expression of αLNNd in dy2J mice resulted in strong amelioration of the dystrophic phenotype, manifested by the prevention of fibrosis and restoration of forelimb grip strength. αLNNd also restored myofiber shape, size, and numbers to control levels in dy2J mice. Laminin immunostaining and quantitation of tissue extractions revealed increased Lm211 expression in αLNNd-transgenic dy2J mice. In cultured myotubes, we determined that αLNNd expression increased myotube surface accumulation of polymerization-deficient recombinant laminins, with retention of collagen IV, reiterating the basement membrane (BM) changes observed in vivo. Laminin LN domain mutations linked to several of the Lmα2-deficient muscular dystrophies are predicted to compromise polymerization. The data herein support the hypothesis that engineered expression of αLNNd can overcome polymerization deficits to increase laminin, stabilize BM structure, and substantially ameliorate muscular dystrophy.

Asunto(s)

Laminina , Distrofia Muscular Animal , Mutación , Miofibrillas , Proteínas Recombinantes de Fusión , Animales , Células HEK293 , Humanos , Laminina/biosíntesis , Laminina/genética , Ratones Transgénicos , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patología , Miofibrillas/metabolismo , Miofibrillas/patología , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética

RESUMEN

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) - regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees' relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees' primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network.

Asunto(s)

Abejas/fisiología , Metilación de ADN , Aprendizaje , Odorantes , Bulbo Olfatorio/fisiología , Animales , Epigénesis Genética , Estudios de Asociación Genética , Memoria , Recompensa

RESUMEN

Honeybees (Apis mellifera) are insects living in colonies with a complex social organization. Their nest contains food stores in the form of honey and pollen, as well as the brood, the queen and the bees themselves. These resources have to be defended against a wide range of predators and parasites, a task that is performed by specialized workers, called guard bees. Guards tune their response to both the nature of the threat and the environmental conditions, in order to achieve an efficient trade-off between defence and loss of foraging workforce. By releasing alarm pheromones, they are able to recruit other bees to help them handle large predators. These chemicals trigger both rapid and longer-term changes in the behaviour of nearby bees, thus priming them for defence. Here, we review our current understanding on how this sequence of events is performed and regulated depending on a variety of factors that are both extrinsic and intrinsic to the colony. We present our current knowledge on the neural bases of honeybee aggression and highlight research avenues for future studies in this area. We present a brief overview of the techniques used to study honeybee aggression, and discuss how these could be used to gain further insights into the mechanisms of this behaviour.

Asunto(s)

Abejas/fisiología , Agresión/efectos de los fármacos , Animales , Jerarquia Social , Feromonas/farmacología , Conducta Predatoria/efectos de los fármacos , Vocalización Animal/efectos de los fármacos

RESUMEN

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

RESUMEN

Recent evidence suggests that olfactory stimuli can influence early stages of visual processing, but there has been little focus on whether such olfactory-visual interactions convey an advantage in visual object identification. Moreover, despite evidence that some aspects of olfactory perception are superior in females than males, no study to date has examined whether olfactory influences on vision are gender-dependent. We asked whether inhalation of familiar odorants can modulate participants' ability to identify briefly flashed images of matching visual objects under conditions of object substitution masking (OSM). Across two experiments, we had male and female participants (N = 36 in each group) identify masked visual images of odour-related objects (e.g., orange, rose, mint) amongst nonodour-related distracters (e.g., box, watch). In each trial, participants inhaled a single odour that either matched or mismatched the masked, odour-related target. Target detection performance was analysed using a signal detection (d') approach. In females, but not males, matching odours significantly reduced OSM relative to mismatching odours, suggesting that familiar odours can enhance the salience of briefly presented visual objects. We conclude that olfactory cues exert a subtle influence on visual processes by transiently enhancing the salience of matching object representations. The results add to a growing body of literature that points towards consistent gender differences in olfactory perception.

Asunto(s)

Señales (Psicología) , Odorantes/análisis , Percepción Olfatoria , Enmascaramiento Perceptual , Estimulación Luminosa/métodos , Adulto , Femenino , Humanos , Masculino , Apego a Objetos , Factores Sexuales , Adulto Joven

RESUMEN

Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine-6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory.

Asunto(s)

Señalización del Calcio , Espinas Dendríticas/fisiología , Hipocampo/metabolismo , Potenciación a Largo Plazo , Proteínas de la Membrana/fisiología , Memoria/fisiología , Animales , Animales Recién Nacidos , Células COS , Chlorocebus aethiops , Ratones Noqueados , Mutagénesis Sitio-Dirigida , Plasticidad Neuronal , Cultivo Primario de Células , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Proteína de Unión al GTP rac1/metabolismo

RESUMEN

Honeybees defend their colonies aggressively against intruders and release a potent alarm pheromone to recruit nestmates into defensive tasks. The effect of floral odours on this behaviour has never been studied, despite the relevance of these olfactory cues for the biology of bees. Here we use a novel assay to investigate social and olfactory cues that drive defensive behaviour in bees. We show that social interactions are necessary to reveal the recruiting function of the alarm pheromone and that specific floral odours-linalool and 2-phenylethanol-have the surprising capacity to block recruitment by the alarm pheromone. This effect is not due to an olfactory masking of the pheromone by the floral odours, but correlates with their appetitive value. In addition to their potential applications, these findings provide new insights about how honeybees make the decision to engage into defence and how conflicting information affects this process.

Asunto(s)

Agresión/fisiología , Abejas/efectos de los fármacos , Abejas/fisiología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Odorantes , Animales , Flores

RESUMEN

DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee.

Asunto(s)

ADN (Citosina-5-)-Metiltransferasas/metabolismo , Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , Animales , Abejas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Citidina/análogos & derivados , Citidina/farmacología , ADN/química , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN/efectos de los fármacos , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Epigénesis Genética , Memoria a Largo Plazo/efectos de los fármacos , Ftalimidas/farmacología , Olfato/fisiología , Triptófano/análogos & derivados , Triptófano/farmacología , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Neurexins are cell adhesion molecules that are important for synaptic plasticity and homeostasis, although links to sleep have not yet been investigated. We examined the effects of neurexin-1 perturbation on sleep in Drosophila, showing that neurexin-1 nulls displayed fragmented sleep and altered circadian rhythm. Conversely, the over-expression of neurexin-1 could increase and consolidate night-time sleep. This was not solely due to developmental effects as it could be induced acutely in adulthood, and was coupled with evidence of synaptic growth. The timing of over-expression could differentially impact sleep patterns, with specific night-time effects. These results show that neurexin-1 was dynamically involved in synaptic plasticity and sleep in Drosophila. Neurexin-1 and a number of its binding partners have been repeatedly associated with mental health disorders, including autism spectrum disorders, schizophrenia and Tourette syndrome, all of which are also linked to altered sleep patterns. How and when plasticity-related proteins such as neurexin-1 function during sleep can provide vital information on the interaction between synaptic homeostasis and sleep, paving the way for more informed treatments of human disorders.

Asunto(s)

Moléculas de Adhesión Celular Neuronal/fisiología , Ritmo Circadiano/fisiología , Proteínas de Drosophila/fisiología , Drosophila melanogaster/fisiología , Plasticidad Neuronal/fisiología , Sueño/fisiología , Animales , Conducta Animal/fisiología , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de Drosophila/metabolismo

RESUMEN

The existence of 'false memories', where individuals remember events that they have never actually experienced, is well established in humans. Now a new study reports that insects similarly form illusory memories through merging of memory traces.

Asunto(s)

Abejas/fisiología , Memoria/fisiología , Animales , Cognición/fisiología , Humanos , Modelos Animales

RESUMEN

Sensory information is initially registered within anatomically and functionally segregated brain networks but is also integrated across modalities in higher cortical areas. Although considerable research has focused on uncovering the neural correlates of multisensory integration for the modalities of vision, audition, and touch, much less attention has been devoted to understanding interactions between vision and olfaction in humans. In this study, we asked how odors affect neural activity evoked by images of familiar visual objects associated with characteristic smells. We employed scalp-recorded EEG to measure visual ERPs evoked by briefly presented pictures of familiar objects, such as an orange, mint leaves, or a rose. During presentation of each visual stimulus, participants inhaled either a matching odor, a nonmatching odor, or plain air. The N1 component of the visual ERP was significantly enhanced for matching odors in women, but not in men. This is consistent with evidence that women are superior in detecting, discriminating, and identifying odors and that they have a higher gray matter concentration in olfactory areas of the OFC. We conclude that early visual processing is influenced by olfactory cues because of associations between odors and the objects that emit them, and that these associations are stronger in women than in men.

Asunto(s)

Atención/fisiología , Mapeo Encefálico , Señales (Psicología) , Potenciales Evocados Visuales/fisiología , Olfato/fisiología , Adulto , Discriminación en Psicología/fisiología , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Odorantes , Reconocimiento Visual de Modelos/fisiología , Factores Sexuales , Adulto Joven