RESUMEN

The pulsatile activity of gonadotropin-releasing hormone neurons (GnRH neurons) is a key factor in the regulation of reproductive hormones. This pulsatility is orchestrated by a network of neurons that release the neurotransmitters kisspeptin, neurokinin B, and dynorphin (KNDy neurons), and produce episodic bursts of activity driving the GnRH neurons. We show in this computational study that the features of coordinated KNDy neuron activity can be explained by a neural network in which connectivity among neurons is modular. That is, a network structure consisting of clusters of highly-connected neurons with sparse coupling among the clusters. This modular structure, with distinct parameters for intracluster and intercluster coupling, also yields predictions for the differential effects on synchronization of changes in the coupling strength within clusters versus between clusters.

Asunto(s)

Dinorfinas , Hormona Liberadora de Gonadotropina , Modelos Neurológicos , Red Nerviosa , Neuronas , Neuronas/fisiología , Red Nerviosa/fisiología , Animales , Dinorfinas/metabolismo , Dinorfinas/fisiología , Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Kisspeptinas/fisiología , Neuroquinina B/metabolismo , Neuroquinina B/fisiología , Biología Computacional , Potenciales de Acción/fisiología , Simulación por Computador , Humanos

RESUMEN

Computational experiments have been very important to numerically simulate real phenomena in several areas. Many studies in computational biology discuss the necessity to obtain numerical replicability to accomplish new investigations. However, even following well-established rules in the literature, numerical replicability is unsuccessful when it takes the computer's limitations for representing real numbers into consideration. In this study, we used a previous published recurrent network model composed by Hodgkin-Huxley-type neurons to simulate the neural activity during development. The original source code in C/C++ was carefully refactored to mitigate the lack of replicability; moreover, it was re-implemented to other programming languages/software (XPP/XPPAUT, Python and Matlab) and executed under two operating systems (Windows and Linux). The commutation and association of the input current values during the summation of the pre-synaptic activity were also analyzed. A total of 72 simulations which must obtain the same result were executed to cover these scenarios. The results were replicated when the high floating-point precision (supplied by third-party libraries) was used. However, using the default floating-point precision type, none of the results were replicated when compared with previous results. Several new procedures were proposed during the source code refactorization; they allowed replicating only a few scenarios, regardless of the language and operating system. Thus, the generated computational "errors" were the same. Even using a simple computational model, the numerical replicability was very difficult to be achieved, requiring people with computational expertise to be performed. After all, the research community must be aware that conducting analyses with numerical simulations that use real number operations can lead to different conclusions.

RESUMEN

Previous observations suggest the existence of 'Active sleep' in cephalopods. To investigate in detail the behavioral structure of cephalopod sleep, we video-recorded four adult specimens of Octopus insularis and quantified their distinct states and transitions. Changes in skin color and texture and movements of eyes and mantle were assessed using automated image processing tools, and arousal threshold was measured using sensory stimulation. Two distinct states unresponsive to stimulation occurred in tandem. The first was a 'Quiet sleep' state with uniformly pale skin, closed pupils, and long episode durations (median 415.2 s). The second was an 'Active sleep' state with dynamic skin patterns of color and texture, rapid eye movements, and short episode durations (median 40.8 s). 'Active sleep' was periodic (60% of recurrences between 26 and 39 min) and occurred mostly after 'Quiet sleep' (82% of transitions). These results suggest that cephalopods have an ultradian sleep cycle analogous to that of amniotes.

RESUMEN

Food allergy is 1 of the 4 manifestations of the "atopic march," along with eczema, allergic rhinitis, and asthma. Depending on the pathophysiologic immune mechanisms behind a food allergy, it can be classified as immunoglobulin E-mediated, non-immunoglobulin E-mediated, or mixed. The prevalence of food allergies has risen worldwide during the past few decades, becoming a significant global health concern. Patients experiencing food allergies and their caregivers are heavily burdened personally, socially, emotionally, and financially. The health-care system is also considerably affected. Pediatricians, as primary health-care providers, are often challenged with these patients, becoming the first-line for the recognition and management of food allergies. The purpose of this review is to provide a comprehensive summary of food allergies, including the most up-to-date information, recent guidelines, and recommendations.

Asunto(s)

Hipersensibilidad a los Alimentos , Adolescente , Anafilaxia/diagnóstico , Anafilaxia/etiología , Anafilaxia/terapia , Niño , Preescolar , Diagnóstico Diferencial , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Hipersensibilidad a los Alimentos/terapia , Humanos , Lactante , Desnutrición/diagnóstico , Desnutrición/etiología , Desnutrición/terapia , Pediatría , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud , Pronóstico , Calidad de Vida , Derivación y Consulta , Factores de Riesgo , Estados Unidos/epidemiología

RESUMEN

Building upon previous experiments can be used to accomplish new goals. In computing, it is imperative to reuse computer code to continue development on specific projects. Reproducibility is a fundamental building block in science, and experimental reproducibility issues have recently been of great concern. It may be surprising that reproducibility is also of concern in computational science. In this study, we used a previously published code to investigate neural network activity and we were unable to replicate our original results. This led us to investigate the code in question, and we found that several different aspects, attributable to floating-point arithmetic, were the cause of these replicability issues. Furthermore, we uncovered other manifestations of this lack of replicability in other parts of the computation with this model. The simulated model is a standard system of ordinary differential equations, very much like those commonly used in computational neuroscience. Thus, we believe that other researchers in the field should be vigilant when using such models and avoid drawing conclusions from calculations if their qualitative results can be substantially modified through non-reproducible circumstances.

Asunto(s)

Neuronas/fisiología , Simulación por Computador , Modelos Neurológicos , Redes Neurales de la Computación , Reproducibilidad de los Resultados

RESUMEN

The gain of transcription factor binding sites (TFBS) is believed to represent one of the major causes of biological innovation. Here we used strategies based on comparative genomics to identify 21,822 TFBS specific to the human lineage (TFBS-HS), when compared to chimpanzee and gorilla genomes. More than 40% (9,206) of these TFBS-HS are in the vicinity of 1,283 genes. A comparison of the expression pattern of these genes and the corresponding orthologs in chimpanzee and gorilla identified genes differentially expressed in human tissues. These genes show a more divergent expression pattern in the human testis and brain, suggesting a role for positive selection in the fixation of TFBS gains. Genes associated with TFBS-HS were enriched in gene ontology categories related to transcriptional regulation, signaling, differentiation/development and nervous system. Furthermore, genes associated with TFBS-HS present a higher expression breadth when compared to genes in general. This biased distribution is due to a preferential gain of TFBS in genes with higher expression breadth rather than a shift in the expression pattern after the gain of TFBS.

Asunto(s)

Encéfalo/metabolismo , Testículo/metabolismo , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , Evolución Biológica , Regulación de la Expresión Génica , Ontología de Genes , Genoma Humano/genética , Genómica , Gorilla gorilla/genética , Humanos , Masculino , Especificidad de Órganos , Pan troglodytes/genética , Regiones Promotoras Genéticas , Especificidad de la Especie

RESUMEN

The brain stores memories by persistently changing the connectivity between neurons. Sleep is known to be critical for these changes to endure. Research on the neurobiology of sleep and the mechanisms of long-term synaptic plasticity has provided data in support of various theories of how brain activity during sleep affects long-term synaptic plasticity. The experimental findings - and therefore the theories - are apparently quite contradictory, with some evidence pointing to a role of sleep in the forgetting of irrelevant memories, whereas other results indicate that sleep supports the reinforcement of the most valuable recollections. A unified theoretical framework is in need. Computational modeling and simulation provide grounds for the quantitative testing and comparison of theoretical predictions and observed data, and might serve as a strategy to organize the rather complicated and diverse pool of data and methodologies used in sleep research. This review article outlines the emerging progress in the computational modeling and simulation of the main theories on the role of sleep in memory consolidation.

Asunto(s)

Encéfalo/fisiología , Simulación por Computador , Homeostasis/fisiología , Potenciación a Largo Plazo/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Consolidación de la Memoria/fisiología , Modelos Teóricos , Fases del Sueño/fisiología , Humanos

RESUMEN

Early in development, neural systems have primarily excitatory coupling, where even GABAergic synapses are excitatory. Many of these systems exhibit spontaneous episodes of activity that have been characterized through both experimental and computational studies. As development progress the neural system goes through many changes, including synaptic remodeling, intrinsic plasticity in the ion channel expression, and a transformation of GABAergic synapses from excitatory to inhibitory. What effect each of these, and other, changes have on the network behavior is hard to know from experimental studies since they all happen in parallel. One advantage of a computational approach is that one has the ability to study developmental changes in isolation. Here, we examine the effects of GABAergic synapse polarity change on the spontaneous activity of both a mean field and a neural network model that has both glutamatergic and GABAergic coupling, representative of a developing neural network. We find some intuitive behavioral changes as the GABAergic neurons go from excitatory to inhibitory, shared by both models, such as a decrease in the duration of episodes. We also find some paradoxical changes in the activity that are only present in the neural network model. In particular, we find that during early development the inter-episode durations become longer on average, while later in development they become shorter. In addressing this unexpected finding, we uncover a priming effect that is particularly important for a small subset of neurons, called the "intermediate neurons." We characterize these neurons and demonstrate why they are crucial to episode initiation, and why the paradoxical behavioral change result from priming of these neurons. The study illustrates how even arguably the simplest of developmental changes that occurs in neural systems can present non-intuitive behaviors. It also makes predictions about neural network behavioral changes that occur during development that may be observable even in actual neural systems where these changes are convoluted with changes in synaptic connectivity and intrinsic neural plasticity.

RESUMEN

It is widely accepted that cortical neurons are similarly more activated during waking and paradoxical sleep (PS; aka REM) than during slow-wave sleep (SWS). However, we recently reported using Fos labeling that only a few limbic cortical structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) contain a large number of neurons activated during PS hypersomnia. Our aim in the present study was to record local field potentials and unit activity from these two structures across all vigilance states in freely moving male rats to determine whether the RSC and the ACA are electrophysiologically specifically active during basal PS episodes. We found that theta power was significantly higher during PS than during active waking (aWK) similarly in the RSC and hippocampus (HPC) but not in ACA. Phase-amplitude coupling between HPC theta and gamma oscillations strongly and specifically increased in RSC during PS compared with aWK. It did not occur in ACA. Further, 68% and 43% of the units recorded in the RSC and ACA were significantly more active during PS than during aWK and SWS, respectively. In addition, neuronal discharge of RSC but not of ACA neurons increased just after the peak of hippocampal theta wave. Our results show for the first time that RSC neurons display enhanced spiking in synchrony with theta specifically during PS. We propose that activation of RSC neurons specifically during PS may play a role in the offline consolidation of spatial memories, and in the generation of vivid perceptual scenery during dreaming.SIGNIFICANCE STATEMENT Fifty years ago, Michel Jouvet used the term paradoxical to define REM sleep because of the simultaneous occurrence of a cortical activation similar to waking accompanied by muscle atonia. However, we recently demonstrated using functional neuroanatomy that only a few limbic structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) are activated during PS. In the present study, we show for the first time that the RSC and ACA contain neurons firing more during PS than in any other state. Further, RSC neurons are firing in phase with the hippocampal theta rhythm. These data indicate that the RSC is very active during PS and could play a key role in memory consolidation taking place during this state.

Asunto(s)

Corteza Cerebral/fisiología , Giro del Cíngulo/fisiología , Hipocampo/fisiología , Sueño REM/fisiología , Ritmo Teta/fisiología , Animales , Fenómenos Electrofisiológicos/fisiología , Masculino , Ratas , Ratas Sprague-Dawley

RESUMEN

During sleep, humans experience the offline images and sensations that we call dreams, which are typically emotional and lacking in rational judgment of their bizarreness. However, during lucid dreaming (LD), subjects know that they are dreaming, and may control oneiric content. Dreaming and LD features have been studied in North Americans, Europeans and Asians, but not among Brazilians, the largest population in Latin America. Here we investigated dreams and LD characteristics in a Brazilian sample (n = 3,427; median age = 25 years) through an online survey. The subjects reported recalling dreams at least once a week (76%), and that dreams typically depicted actions (93%), known people (92%), sounds/voices (78%), and colored images (76%). The oneiric content was associated with plans for the upcoming days (37%), memories of the previous day (13%), or unrelated to the dreamer (30%). Nightmares usually depicted anxiety/fear (65%), being stalked (48%), or other unpleasant sensations (47%). These data corroborate Freudian notion of day residue in dreams, and suggest that dreams and nightmares are simulations of life situations that are related to our psychobiological integrity. Regarding LD, we observed that 77% of the subjects experienced LD at least once in life (44% up to 10 episodes ever), and for 48% LD subjectively lasted less than 1 min. LD frequency correlated weakly with dream recall frequency (r = 0.20, p < 0.01), and LD control was rare (29%). LD occurrence was facilitated when subjects did not need to wake up early (38%), a situation that increases rapid eye movement sleep (REMS) duration, or when subjects were under stress (30%), which increases REMS transitions into waking. These results indicate that LD is relatively ubiquitous but rare, unstable, difficult to control, and facilitated by increases in REMS duration and transitions to wake state. Together with LD incidence in USA, Europe and Asia, our data from Latin America strengthen the notion that LD is a general phenomenon of the human species.