The Activity of Anandamide at Vanilloid VR1 Receptors Requires Facilitated Transport across the Cell Membrane and Is Limited by Intracellular Metabolism

The endogenous ligand of CB(1) cannabinoid receptors, anandamide, is also a full agonist at vanilloid VR1 receptors for capsaicin and resiniferatoxin, thereby causing an increase in cytosolic Ca(2+) concentration in human VR1-overexpressing (hVR1-HEK) cells. Two selective inhibitors of anandamide facilitated transport into cells, VDM11 and VDM13, and two inhibitors of anandamide enzymatic hydrolysis, phenylmethylsulfonyl fluoride and methylarachidonoyl fluorophosphonate, inhibited and enhanced, respectively, the VR1-mediated effect of anandamide, but not of resiniferatoxin or capsaicin. The nitric oxide donor, sodium nitroprusside, known to stimulate anandamide transport, enhanced anandamide effect on the cytosolic Ca(2+) concentration. Accordingly, hVR1-HEK cells contain an anandamide membrane transporter inhibited by VDM11 and VDM13 and activated by sodium nitroprusside, and an anandamide hydrolase activity sensitive to phenylmethylsulfonyl fluoride and methylarachidonoyl fluorophosphonate, and a fatty acid amide hydrolase transcript. These findings suggest the following. (i) Anandamide activates VR1 receptors by acting at an intracellular site. (ii) Degradation by fatty acid amide hydrolase limits anandamide activity on VR1; and (iii) the anandamide membrane transporter inhibitors can be used to distinguish between CB(1) or VR1 receptor-mediated actions of anandamide. By contrast, the CB(1) receptor antagonist SR141716A inhibited also the VR1-mediated effect of anandamide and capsaicin on cytosolic Ca(2+) concentration, although at concentrations higher than those required for CB(1) antagonism

Eye-specific detection and a multi-eye integration model of biological motion perception

‘Biological motion’ refers to the distinctive kinematics observed in many living organisms, where visually perceivable points on the animal move at fixed distances from each other. Across the animal kingdom, many species have developed specialized visual circuitry to recognize such biological motion and to discriminate it from other patterns. Recently, this ability has been observed in the distributed visual system of jumping spiders. These eight-eyed animals use six eyes to perceive motion, while the remaining two (the principal anterior medial eyes) are shifted across the visual scene to further inspect detected objects. When presented with a biologically moving stimulus and a random one, jumping spiders turn to face the latter, clearly demonstrating the ability to discriminate between them. However, it remains unclear whether the principal eyes are necessary for this behavior, whether all secondary eyes can perform this discrimination, or whether a single eye-pair is specialized for this task. Here, we systematically tested the ability of jumping spiders to discriminate between biological and random visual stimuli by testing each eye-pair alone. Spiders were able to discriminate stimuli only when the anterior lateral eyes were unblocked, and performed at chance levels in other configurations. Interestingly, spiders showed a preference for biological motion over random stimuli – unlike in past work. We therefore propose a new model describing how specialization of the anterior lateral eyes for detecting biological motion contributes to multi-eye integration in this system. This integration generates more complex behavior through the combination of simple, single-eye responses. We posit that this in-built modularity may be a solution to the limited resources of these invertebrates' brains, constituting a novel approach to visual processing

Irrational risk aversion in an ant

Animals must often decide between exploiting safe options or risky options with a chance for large gains. Both proximate theories based on perceptual mechanisms, and evolutionary ones based on fitness benefits, have been proposed to explain decisions under risk. Eusocial insects represent a special case of risk sensitivity, as they must often make collective decisions based on resource evaluations from many individuals. Previously, colonies of the ant Lasius niger were found to be risk-neutral, but the risk preference of individual foragers was unknown. Here, we tested individual L. niger in a risk sensitivity paradigm. Ants were trained to associate one scent with 0.55 M sucrose solution and another with an equal chance of either 0.1 or 1.0 M sucrose. Preference was tested in a Y-maze. Ants were extremely risk-averse, with 91% choosing the safe option. Based on the psychophysical Weber–Fechner law, we predicted that ants evaluate resources depending on their logarithmic difference. To test this hypothesis, we designed 4 more experiments by varying the relative differences between the alternatives, making the risky option less, equally or more valuable than the safe one. Our results support the logarithmic origin of risk aversion in ants, and demonstrate that the behaviour of individual foragers can be a very poor predictor of colony-level behaviour

Perception of biological motion by jumping spiders

The body of most creatures is composed of interconnected joints. During motion, the spatial location of these joints changes, but they must maintain their distances to one another, effectively moving semirigidly. This pattern, termed “biological motion” in the literature, can be used as a visual cue, enabling many animals (including humans) to distinguish animate from inanimate objects. Crucially, even artificially created scrambled stimuli, with no recognizable structure but that maintains semirigid movement patterns, are perceived as animated. However, to date, biological motion perception has only been reported in vertebrates. Due to their highly developed visual system and complex visual behaviors, we investigated the capability of jumping spiders to discriminate biological from nonbiological motion using point-light display stimuli. These kinds of stimuli maintain motion information while being devoid of structure. By constraining spiders on a spherical treadmill, we simultaneously presented 2 point-light displays with specific dynamic traits and registered their preference by observing which pattern they turned toward. Spiders clearly demonstrated the ability to discriminate between biological motion and random stimuli, but curiously turned preferentially toward the latter. However, they showed no preference between biological and scrambled displays, results that match responses produced by vertebrates. Crucially, spiders turned toward the stimuli when these were only visible by the lateral eyes, evidence that this task may be eye specific. This represents the first demonstration of biological motion recognition in an invertebrate, posing crucial questions about the evolutionary history of this ability and complex visual processing in nonvertebrate systems

Acute exposure to caffeine improves foraging in an invasive ant

Argentine ants, Linepithema humile, are a particularly concerning invasive species. Control efforts often fall short likely due to a lack of sustained bait consumption. Using neuroactives, such as caffeine, to improve ant learning and navigation could increase recruitment and consumption of toxic baits. Here, we exposed L. humile to a range of caffeine concentrations and a complex ecologically relevant task: an open landscape foraging experiment. Without caffeine, we found no effect of consecutive foraging visits on the time the ants take to reach a reward, suggesting a failure to learn the reward’s location. However, under low to intermediate caffeine concentrations ants were 38% faster with each consecutive visit, implying that caffeine boosts learning. Interestingly, such improvements were lost at high doses. In contrast, caffeine had no impact on the ants’ homing behavior. Adding moderate levels of caffeine to baits could improve ant’s ability to learn its location, improving bait efficacy

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

Copy when uncertain: lower light levels increase trail pheromone deposition and reliance on pheromone trails in ants

Animals may gather information from multiple sources, and these information sources may conflict. Theory predicts that, all else being equal, reliance on a particular information source will depend on its information content relative to other sources. Information conflicts are a good area in which to test such predictions. Social insects, such as ants, make extensive use of both private information (e.g. visual route memories) and social information (e.g. pheromone trails) when attempting to locate a food source. Importantly, eusocial insects collaborate on food retrieval, so both information use and information provision may be expected to vary with the information content of alternative information sources. Many ants, such as Lasius niger, are active both day and night. Variation in light levels represents an ecologically important change in the information content of visually-acquired route information. Here, we examine information use and information provision under high light levels (3200 lux, equivalent to a bright but overcast day), moderate light levels simulating dusk (10 lux) and darkness (0.007 lux, equivalent to a moonless night). Ants learn poorly, or not at all, in darkness. As light levels decrease, ants show decreasing reliance on private visual information, and a stronger reliance on social information, consistent with a ‘copy when uncertain’ strategy. In moderate light levels and darkness, pheromone deposition increases, presumably to compensate for the low information content of visual information. Varying light levels for cathemeral animals provides a powerful and ecologically meaningful method for examining information use and provision under varying levels of information content

Brain miniaturization and its implications for cognition: evidence from Salticidae and Hymenoptera

Scientists have always been fascinated and puzzled by the marvel that is the human brain. This organ seems to be of an exaggerated size for our body, demanding an enormous amount of energy and resources to be maintained. For evolution to favour such an enormous expenditure of energy, the benefits must outweigh the cost. During the history of neuroscience different authors have attempted to correlate the size of a species nervous system with its cognitive abilities, in the search for an explanation on why we have such a big brain: if possessing an oversized brain is how a species can produce outstanding cognitive abilities, then the survival advantage outweighs the costs. However, brain size correlates first of all with body size, having nothing to do with the cognitive capabilities of a species. To solve this problem, different measures have been adopted, like brain-to- body weight ratio, encephalization quotient, the raw number of neurons in the cortical areas. When confronted with empirical evidence, however, all these measures fail to predict the presence of complex cognition, especially for species phylogenetically distant from us. In particular, miniaturized organisms, like insects or spiders, exhibit outstanding behaviours, products of complex cognition, with brains multiple orders of magnitude smaller than ours. It has been proposed that our premise is misguided. Cognition does not need a big brain to manifest, quite the opposite: a higher number of neurons increase the memory buffer and becomes more robust against noise, while cognitive processes only require a handful of cells well organized in complex circuits. The process of brain miniaturization during evolution should have favoured the birth of small but complex neural circuits, capable of dealing with multiple situations. In this framework, in this thesis, I have presented some of the studies carried out during my PhD project on miniature organisms. Firstly, the ants are described. As these insects are phylogenetically similar to bees and bumblebees, which have been extensively studied in the last three decades and have been found capable of outstanding cognitive processes, they represent the first candidate to understand if complex cognition is widespread in invertebrates With two different studies, we tested the ability of ants to perceive and register information from the environment. It appears that the process of miniaturization during evolution has favoured the development of clever circuitry, that let the ants process a great variety of information with only a handful of neurons, and register those with a load-independent memory process, suggesting the presence of complex cognitive abilities. Secondly, as the main topic of my project, the jumping spiders are presented. These arachnids have recently caught the interest of scientists for their unique hunting strategies, that involve detouring perspective taking, categorization and other cognitive skills. I have tested their visual perception to understand if it is guided by the same rules that govern the human’s one (e.g., Gestalt principles). However, I failed to design a methodology capable to consistently train the spiders, and as such the results were inconclusive. To overcome this problem, I designed an automated training system. This proved to be an effective way to train jumping spiders, opening future possibilities for the study of this species’ cognitive abilities

Brain miniaturization and its implications for cognition: evidence from Salticidae and Hymenoptera

Scientists have always been fascinated and puzzled by the marvel that is the human brain. This organ seems to be of an exaggerated size for our body, demanding an enormous amount of energy and resources to be maintained. For evolution to favour such an enormous expenditure of energy, the benefits must outweigh the cost. During the history of neuroscience different authors have attempted to correlate the size of a species nervous system with its cognitive abilities, in the search for an explanation on why we have such a big brain: if possessing an oversized brain is how a species can produce outstanding cognitive abilities, then the survival advantage outweighs the costs. However, brain size correlates first of all with body size, having nothing to do with the cognitive capabilities of a species. To solve this problem, different measures have been adopted, like brain-to- body weight ratio, encephalization quotient, the raw number of neurons in the cortical areas. When confronted with empirical evidence, however, all these measures fail to predict the presence of complex cognition, especially for species phylogenetically distant from us. In particular, miniaturized organisms, like insects or spiders, exhibit outstanding behaviours, products of complex cognition, with brains multiple orders of magnitude smaller than ours. It has been proposed that our premise is misguided. Cognition does not need a big brain to manifest, quite the opposite: a higher number of neurons increase the memory buffer and becomes more robust against noise, while cognitive processes only require a handful of cells well organized in complex circuits. The process of brain miniaturization during evolution should have favoured the birth of small but complex neural circuits, capable of dealing with multiple situations. In this framework, in this thesis, I have presented some of the studies carried out during my PhD project on miniature organisms. Firstly, the ants are described. As these insects are phylogenetically similar to bees and bumblebees, which have been extensively studied in the last three decades and have been found capable of outstanding cognitive processes, they represent the first candidate to understand if complex cognition is widespread in invertebrates With two different studies, we tested the ability of ants to perceive and register information from the environment. It appears that the process of miniaturization during evolution has favoured the development of clever circuitry, that let the ants process a great variety of information with only a handful of neurons, and register those with a load-independent memory process, suggesting the presence of complex cognitive abilities. Secondly, as the main topic of my project, the jumping spiders are presented. These arachnids have recently caught the interest of scientists for their unique hunting strategies, that involve detouring perspective taking, categorization and other cognitive skills. I have tested their visual perception to understand if it is guided by the same rules that govern the human’s one (e.g., Gestalt principles). However, I failed to design a methodology capable to consistently train the spiders, and as such the results were inconclusive. To overcome this problem, I designed an automated training system. This proved to be an effective way to train jumping spiders, opening future possibilities for the study of this species’ cognitive abilities