Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report

BackgroundTherapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses.Case presentationA Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L−1, p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises.ConclusionsPeople with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis

Uso de fármacos psicoestimulantes en drogodependencias

El uso de medicamentos estimulantes es una cuestión de plena actualidad en psiquiatría, aunque su utilización y prescripción es controvertida . Fármacos como el metilfenidato, las anfetaminas, o el modafinilo están siendo utilizados y estudiados en distintas enfermedades psiquiátricas como el trastorno por déficit de atención e hiperactividad (TDAH), la dependencia de cocaína, en trastornos del sueño y en la depresión resistente. Todos estos fármacos tienen en común, igual que las drogas de abuso, que son medicamentos que actúan sobre el sistema dopaminérgico, que constituye la base neurobiológica del refuerzo fisiológico. Los estimulantes como el metilfenidato o el modafinilo son fármacos eficaces en el TDAH y han sido estudiados en el tratamiento de la dependencia de cocaína. En niños con TDAH el metilfenidato es un factor protector para el desarrollo de fármaco en la dependencia de cocaína, aunque son estudios preliminares, por lo que no se debe considerar que este totalmente demostrado que los fármacos psicoestimulantes sean eficaces en el tratamiento de esta dependencia. Aunque no son conocidos todos los mecanismos fisiopatológicos, parece crítico que el refuerzo, y por lo tanto el riesgo de dependencia, aparece cuando se producen incrementos rápidos dopaminérgicos y que los efectos terapéuticos aparecen cuando son lentos y mantenidos. Las características de uso a dosis bajas administradas por vía oral disminuyen el riesgo de abuso. Para realizar una adecuada prescripción es necesario aclarar, definitivamente, los mecanismos neuroquímicos en los que intervienen, y sus indicaciones en drogodependenciasStimulant drugs prescription is a controversial and current topic in psychiatry. Drugs such as methylphenidate, amphetamine compounds and modafinil have been trialed and used in attention deficit hyperactivity disorder (ADHD), sleep conditions, cocaine dependence and as an adjunct to antidepressants for depression. All these drugs, like stimulant drugs abuse, increase extracellular dopamine in the brain.This effect is associated with reinforcing as well as therapeutic effects. Methylphenidate and modafinil treatment of ADHD are associated with a reduced risk for later substance abuse among ADHD patients. There is evidence of the beneficial effects of the use of modafinil in cocaine dependence, altough there isn't conclusive evidence for the stimulants' efficacy in treatment of the stimulants' dependence. At this time, the physiopathology of drug abuse and dependence is unknown, but it's known that the very critical point is that the reinforcing effects are associated with rapid changes in dopamine increases, whereas the therapeutic effects are associated with slowly and smoothly rising dopamine levels, such as are achieved with low doses and oral administration. Due to this, it's necessary to study the neurobiological bases on which stimulants drugs are related, and their clinical use in dependence treatment

Chromosomal disorders:estimating baseline birth prevalence and pregnancy outcomes worldwide

Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders

Impact of technology-based interventions for children and young people with type 1 diabetes on key diabetes self-management behaviours and prerequisites: A systematic review

Background The role of technology in the self-management of type 1 diabetes mellitus (T1DM) among children and young people is not well understood. Interventions should aim to improve key diabetes self-management behaviours (self-management of blood glucose, insulin administration, physical activity and dietary behaviours) and prerequisites (psychological outcomes and HbA1c) highlighted in the UK guidelines of the National Institute for Health and Care Excellence (NICE) for management of T1DM. The purpose was to identify evidence to assess the effectiveness of technological tools in promoting aspects of these guidelines amongst children and young people. Methods A systematic review of English language articles was conducted using the following databases: Web of Science, PubMed, Scopus, NUSearch, SAGE Journals, SpringerLink, Google Scholar, Science Direct, Sport Discus, Embase, Psychinfo and Cochrane Trials. Search terms included paediatric, type one diabetes, technology, intervention and various synonyms. Included studies examined interventions which supplemented usual care with a health care strategy primarily delivered through a technology-based medium (e.g. mobile phone, website, activity monitor) with the aim of engaging children and young people with T1DM directly in their diabetes healthcare. Studies did not need to include a comparator condition and could be randomised, non-randomised or cohort studies but not single-case studies. Results Of 30 included studies (21 RCTs), the majority measured self-monitoring of blood glucose monitoring (SMBG) frequency, clinical indicators of diabetes self-management (e.g. HbA1c) and/or psychological or cognitive outcomes. The most positive findings were associated with technology-based health interventions targeting SMBG as a behavioural outcome, with some benefits found for clinical and/or psychological diabetes self-management outcomes. Technological interventions were well accepted by children and young people. For the majority of included outcomes, clinical relevance was deemed to be little or none. Conclusions More research is required to assess which elements of interventions are most likely to produce beneficial behavioural outcomes. To produce clinically relevant outcomes, interventions may need to be delivered for at least 1 year and should consider targeting individuals with poorly managed diabetes. It is not possible to determine the impact of technology-based interventions on insulin administration, dietary habits and/or physical activity behaviour due to lack of evidence

Genetic Modulation of Rpd3 Expression Impairs Long-Term Courtship Memory in Drosophila

There is increasing evidence that regulation of local chromatin structure is a critical mechanism underlying the consolidation of long-term memory (LTM), however considerably less is understood about the specific mechanisms by which these epigenetic effects are mediated. Furthermore, the importance of histone acetylation in Drosophila memory has not been reported. The histone deacetylase (HDAC) Rpd3 is abundant in the adult fly brain, suggesting a post-mitotic function. Here, we investigated the role of Rpd3 in long-term courtship memory in Drosophila. We found that while modulation of Rpd3 levels predominantly in the adult mushroom body had no observed impact on immediate recall or one-hour memory, 24-hour LTM was severely impaired. Surprisingly, both overexpression as well as RNAi-mediated knockdown of Rpd3 resulted in impairment of long-term courtship memory, suggesting that the dose of Rpd3 is critical for normal LTM

Brief Exposure to Sensory Cues Elicits Stimulus-Nonspecific General Sensitization in an Insect

The effect of repeated exposure to sensory stimuli, with or without reward is well known to induce stimulus-specific modifications of behaviour, described as different forms of learning. In recent studies we showed that a brief single pre-exposure to the female-produced sex pheromone or even a predator sound can increase the behavioural and central nervous responses to this pheromone in males of the noctuid moth Spodoptera littoralis. To investigate if this increase in sensitivity might be restricted to the pheromone system or is a form of general sensitization, we studied here if a brief pre-exposure to stimuli of different modalities can reciprocally change behavioural and physiological responses to olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and subsequent behavioural tests were carried out to reveal possible intra- and cross-modal effects. Attraction to pheromone, monitored with a locomotion compensator, increased after exposure to olfactory and gustatory stimuli. Behavioural responses to sucrose, investigated using the proboscis extension reflex, increased equally after pre-exposure to olfactory and gustatory cues. Pheromone-specific neurons in the brain and antennal gustatory neurons did, however, not change their sensitivity after sucrose exposure. The observed intra- and reciprocal cross-modal effects of pre-exposure may represent a new form of stimulus-nonspecific general sensitization originating from modifications at higher sensory processing levels

Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction

Die Balanced Scorecard (BSC) als Instrument zur Umsetzung von eLearning in einer phoniatrisch-pädaudologischen Klinik

Die eLearning-Wissensvermittlung im Fach Phoniatrie und Pädaudiologie an der Charité-Universitätsmedizin Berlin steht im Kontext mit der neuen Studienordnung und dem neuen Curriculum für den Regelstudiengang Medizin und zielt ab auf eine solide Grundlage für weitere Modernisierung und Qualitätsoptimierung der Lehre. Der neuen Lehr- und Lernkultur folgend, soll der Regelstudiengang Medizin ein möglichst praxisnahes und lernorientiertes Ausbildungsprofil erhalten. Die Steigerung der Effizienz und Qualität der Lehre soll durch die Nutzung elektronischer Lehr- und Lerntechnologien erhöht werden. Zur erfolgreichen Realisierung ist eLearning als strategisch-integrativer Prozess im Fakultätskonzept der Charité verankert. Die Balanced Scorecard (BSC) wurde als geeignetes Instrument zur Umsetzung der eLearning-Strategie identifiziert, um Strukturen zu schaffen, eLearning langfristig in der universitären Lehre zu etablieren, ferner die Nachhaltigkeit zu optimieren und eLearning in dem Gesamtkonzept der medizinischen Ausbildung zu verankern. Die Balanced Scorecard stellt eine Fortführung und Konkretisierung finanzwirtschaftlicher Kennzahlensysteme dar. Sie verbindet strategisches Management mit traditionellen Kennzahlen indem sie gleichzeitig und balanciert die vier Dimensionen Mitarbeiter, Prozesse/Produkte, Kunden/Markt und Finanzen einbezieht und auf Ursachen-Wirkungsketten basiert. Erste Ergebnisse zeigen, dass die BSC in der Lage ist, die Umsetzung der Unternehmenskonzepte auch für nachgeordnete Strukturen transparenter darzustellen und die Steuerung der Prozesse anhand von Messgrößen zu vereinfachen. Es wird davon ausgegangen, dass die Umsetzung der BSC an der Fakultät einen maßgeblichen Beitrag zum Transfer des eLearning in die Lehre und zur Nachhaltigkeit leistet