Honeybees Learn Odour Mixtures via a Selection of Key Odorants

BACKGROUND The honeybee has to detect, process and learn numerous complex odours from her natural environment on a daily basis. Most of these odours are floral scents, which are mixtures of dozens of different odorants. To date, it is still unclear how the bee brain unravels the complex information contained in scent mixtures. METHODOLOGY/PRINCIPAL FINDINGS This study investigates learning of complex odour mixtures in honeybees using a simple olfactory conditioning procedure, the Proboscis-Extension-Reflex (PER) paradigm. Restrained honeybees were trained to three scent mixtures composed of 14 floral odorants each, and then tested with the individual odorants of each mixture. Bees did not respond to all odorants of a mixture equally: They responded well to a selection of key odorants, which were unique for each of the three scent mixtures. Bees showed less or very little response to the other odorants of the mixtures. The bees' response to mixtures composed of only the key odorants was as good as to the original mixtures of 14 odorants. A mixture composed of the other, non-key-odorants elicited a significantly lower response. Neither an odorant's volatility or molecular structure, nor learning efficiencies for individual odorants affected whether an odorant became a key odorant for a particular mixture. Odorant concentration had a positive effect, with odorants at high concentration likely to become key odorants. CONCLUSIONS/SIGNIFICANCE Our study suggests that the brain processes complex scent mixtures by predominantly learning information from selected key odorants. Our observations on key odorant learning lend significant support to previous work on olfactory learning and mixture processing in honeybees.This work was supported by a grant from the Commonwealth Scientific and Industrial Research Organisation Food Futures Flagship Collaborative Research Fund (CBR3_45865_9 W2003, http://www.csiro.au/org/FoodFuturesFlagship.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS) or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm

DNA methylation and demethylation in honeybee long-term memory formation

Trabalho final de mestrado integrado em Medicina (Cardiologia), apresentado à Faculdade de Medicina da Universidade de Coimbra.A estenose aórtica paradoxal define-se por uma área valvular aórtica ≤ 1 cm2, um volume sistólico indexado < 35 mL/m2 e um gradiente médio transvalvular < 40 mmHg, apesar de uma fração de ejeção do ventrículo esquerdo preservada (> 50%). Caracteriza-se por uma marcada remodelagem concêntrica do ventrículo esquerdo, com predomínio de disfunção diastólica, e está associada a uma rigidez vascular sistémica aumentada. A prevalência desta doença varia entre os 3-35% dos doentes com estenose aórtica grave e afeta sobretudo doentes idosos, do género feminino e com multimorbilidade. A estenose aórtica paradoxal é um desafio diagnóstico, particularmente pelas inconsistências associadas à equação de continuidade. Têm surgido novos métodos de avaliação na literatura para auxiliar no diagnóstico do estado de baixo fluxo sistólico, bem como para estudar a remodelagem ventricular esquerda. Até há pouco tempo existia algum consenso na literatura sobre o facto da estenose aórtica paradoxal representar um estadio mais avançado da doença valvular aórtica. Como tal, na presença de sintomas, a substituição valvular aórtica parecia ser o tratamento mais indicado. No entanto, outros autores mostraram resultados diferentes e assim, aumentaram a discussão sobre a abordagem e gestão deste fenótipo da estenose aórtica degenerativa. A presente tese tem por objetivo elaborar uma revisão sistemática da literatura sobre a estenose aórtica paradoxal, e abordar aspetos relacionados com a sua demografia, semiologia, avaliação diagnóstica, implicações terapêuticas e prognóstico.Paradoxical aortic stenosis is defined by an aortic valve area ≤ 1cm2, an indexed systolic volume < 35 mL/m2 and a transvalvular gradient < 40 mmHg, despite a preserved left ventricular ejection fraction (> 50%). It’s characterized by an extensive concentric cardiac remodelling of the left ventricle, mainly impairing diastolic function, and has been associated with an increased systemic valvular stiffness. This disease prevalence varies from 3 up to 35% of the patients with severe aortic stenosis, specially affecting the elderly, women and those with multi-morbilities. Paradoxical aortic stenosis is a diagnostic challenge due to the inconsistencies associated with the continuity equation. In order to assess the low flow state and to study the left ventricle remodelling, new methods have emerged. Until now there has been some agreement between authors regarding paradoxical aortic stenosis being a more advanced form of aortic valve disease. Hence, in the presence of symptoms, aortic valve replacement presents as an appropriate therapeutic approach. On the contrary, other authors have shown different results, and so fired up the debate concerning the management of this degenerative aortic stenosis phenotype. The aim of the present paper is to systematically review the literature on paradoxical aortic stenosis and to cast light on its demography, semiology, diagnostic workup, therapeutic approach and prognosis

Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera

Vertebrate studies show neuroligins and neurexins are binding partners in a trans-synaptic cell adhesion complex, implicated in human autism and mental retardation disorders. Here we report a genetic analysis of homologous proteins in the honey bee. As in humans, the honeybee has five large (31-246 kb, up to 12 exons each) neuroligin genes, three of which are tightly clustered. RNA analysis of the neuroligin-3 gene reveals five alternatively spliced transcripts, generated through alternative use of exons encoding the cholinesterase-like domain. Whereas vertebrates have three neurexins the bee has just one gene named neurexin I (400 kb, 28 exons). However alternative isoforms of bee neurexin I are generated by differential use of 12 splice sites, mostly located in regions encoding LNS subdomains. Some of the splice variants of bee neurexin I resemble the vertebrate alpha- and beta-neurexins, albeit in vertebrates these forms are generated by alternative promoters. Novel splicing variations in the 3' region generate transcripts encoding alternative trans-membrane and PDZ domains. Another 3' splicing variation predicts soluble neurexin I isoforms. Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults. Transcripts of neurexin I and one neuroligin tested were abundant in mushroom bodies, a higher order processing centre in the bee brain. We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing. Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.Australian National University PhD Scholarship Award to Sunita Biswas

Genetic heterogeneity in autism: from single gene to a pathway perspective

The extreme genetic heterogeneity of autism spectrum disorder (ASD) represents a major challenge. Recent advances in genetic screening and systems biology approaches have extended our knowledge of the genetic etiology of ASD. In this review, we discuss the paradigm shift from a single gene causation model to pathway perturbation model as a guide to better understand the pathophysiology of ASD. We discuss recent genetic findings obtained through next-generation sequencing (NGS) and examine various integrative analyses using systems biology and complex networks approaches that identify convergent patterns of genetic elements associated with ASD

MicroRNA-210 regulates dendritic morphology and behavioural flexibility in mice

MicroRNAs are known to be critical regulators of neuronal plasticity. The highly-conserved, hypoxia- regulated microRNA-210 (miR-210) has been shown to be associated with long term memory in invertebrates and dysregulated in neurodevelopmental and neurodegenerative disease models. However, the role of miR-210 in mammalian neuronal function and cognitive behavior remains unexplored. Here we generated Nestin-cre driven miR-210 neuronal knockout mice to characterise miR-210 regulation and function using in vitro and in vivo methods. We identified miR-210 localisation throughout neuronal somas and dendritic processes and increased levels of mature miR- 210 in response to neural activity in vitro. Loss of miR-210 in neurons resulted in higher oxidative phosphorylation and ROS production following hypoxia and increased dendritic arbour density in hippocampal cultures. Additionally, miR-210 knockout mice displayed altered behavioral flexibility in rodent touchscreen tests, particularly during early reversal learning suggesting processes underlying updating of information and feedback were impacted. Our findings support a conserved, activity- dependent role for miR-210 in neuroplasticity and cognitive function.Australian Research Council (ARC: DP120104117)ARC Future Fellowships (FT110100292; FT140101327)Australian Government Research Training Program StipendAccepte