Institut de Neurosciences Cognitives et Intégratives d’Aquitaine

The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant–herbivore interactions, and provides unique opportunities for developing novel plant protection strategies. The genome of the spider mite Tetranychus urticae is sequenced, providing insights into its polyphagous feeding, silk production, hormonal repertoire and reduced Hox cluster. The spider mite (Tetranychus urticae) is a common agricultural pest that feeds on a wide range of hosts — including maize (corn), soya, tomatoes and peppers — and is notoriously resistant to pesticides. Its genome has now been sequenced and analysed, providing insights into its hormonal repertoire and the evolution of silk production. Transcriptome analysis of mites feeding on different plants reveals how this pest defends itself in a changing host environment and gives pointers to possible non-pesticide plant-protection strategies. The genome encodes 17 fibroin genes, and physical tests of spider-mite silk show it to be a natural nanomaterial with fibres that are more than 100 times thinner than those produced by silk spiders.

In the current global home confinement situation due to the COVID-19 outbreak, most individuals are exposed to an unprecedented stressful situation of unknown duration. This may not only increase daytime stress, anxiety and depression levels, but also disrupt sleep. Importantly, because of the fundamental role that sleep plays in emotion regulation, sleep disturbance can have direct consequences upon next day emotional functioning. In this paper, we summarize what is known about the stress-sleep link and confinement as well as effective insomnia treatment. We discuss those effects of the current home confinement situation that can disrupt sleep but also those that could benefit sleep quality. We suggest adaptions of cognitive behavioural therapy elements that are feasible to implement for those facing changed work schedules and requirements, those with health anxiety and those handling childcare and home-schooling, whilst also recognizing the general limitations imposed on physical exercise and social interaction. Managing sleep problems as best as possible during home confinement can limit stress and possibly prevent disruptions of social relationships.

While necessary from a public health standpoint, Covid-19 confinement strategies are often contrary to evidence-based therapies used to treat mental disorders. University students may be particularly vulnerable to mental health problems, but recent studies have indicated only a negligible impact of confinement strategies. French respondents to a World Mental Health survey of university students completed questions concerning Covid-19 confinement. The sample experienced increased anxiety as well as moderate to severe stress during confinement. Respondents who did not relocate to live with parents were disproportionately affected. Knowledge of confinement effects may be used to reduce its negative impact in vulnerable populations.

As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.

Historically, the thalamus has been viewed as little more than a relay, simply transferring information to key players of the cast, the cortex and hippocampus, without providing any unique functional contribution. In recent years, evidence from multiple laboratories researching different thalamic nuclei has contradicted this idea of the thalamus as a passive structure. Dated models of thalamic functions are being pushed aside, revealing a greater and far more complex contribution of the thalamus for cognition. In this Viewpoints article, we show how recent data support novel views of thalamic functions that emphasize integrative roles in cognition, ranging from learning and memory to flexible adaption. We propose that these apparently separate cognitive functions may indeed be supported by a more general role in shaping mental representations. Several features of thalamocortical circuits are consistent with this suggested role, and we highlight how divergent and convergent thalamocortical and corticothalamic pathways may complement each other to support these functions. Furthermore, the role of the thalamus for subcortical integration is highlighted as a key mechanism for maintaining and updating representations. Finally, we discuss future areas of research and stress the importance of incorporating new experimental findings into existing knowledge to continue developing thalamic models. The presence of thalamic pathology in a number of neurological conditions reinforces the need to better understand the role of this region in cognition.

Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions. In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.

Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state-of-the-art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I-II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.

Fatigue has been defined differently in the literature depending on the field of research. The inconsistent use of the term fatigue complicated scientific communication, thereby limiting progress towards a more in-depth understanding of the phenomenon. Therefore, Enoka and Duchateau (Med Sci Sports Exerc 48:2228-38, 2016, [3]) proposed a fatigue framework that distinguishes between trait fatigue (i.e., fatigue experienced by an individual over a longer period of time) and motor or cognitive task-induced state fatigue (i.e., self-reported disabling symptom derived from the two interdependent attributes performance fatigability and perceived fatigability). Thereby, performance fatigability describes a decrease in an objective performance measure, while perceived fatigability refers to the sensations that regulate the integrity of the performer. Although this framework served as a good starting point to unravel the psychophysiology of fatigue, several important aspects were not included and the interdependence of the mechanisms driving performance fatigability and perceived fatigability were not comprehensively discussed. Therefore, the present narrative review aimed to (1) update the fatigue framework suggested by Enoka and Duchateau (Med Sci Sports Exerc 48:2228-38, 2016, [3]) pertaining the taxonomy (i.e., cognitive performance fatigue and perceived cognitive fatigue were added) and important determinants that were not considered previously (e.g., effort perception, affective valence, self-regulation), (2) discuss the mechanisms underlying performance fatigue and perceived fatigue in response to motor and cognitive tasks as well as their interdependence, and (3) provide recommendations for future research on these interactions. We propose to define motor or cognitive task-induced state fatigue as a psychophysiological condition characterized by a decrease in motor or cognitive performance (i.e., motor or cognitive performance fatigue, respectively) and/or an increased perception of fatigue (i.e., perceived motor or cognitive fatigue). These dimensions are interdependent, hinge on different determinants, and depend on body homeostasis (e.g., wakefulness, core temperature) as well as several modulating factors (e.g., age, sex, diseases, characteristics of the motor or cognitive task). Consequently, there is no single factor primarily determining performance fatigue and perceived fatigue in response to motor or cognitive tasks. Instead, the relative weight of each determinant and their interaction are modulated by several factors.

Anxiety, a behavioral consequence of stress, has been characterized in humans and some vertebrates, but not invertebrates. Here, we demonstrate that after exposure to stress, crayfish sustainably avoided the aversive illuminated arms of an aquatic plus-maze. This behavior was correlated with an increase in brain serotonin and was abolished by the injection of the benzodiazepine anxiolytic chlordiazepoxide. Serotonin injection into unstressed crayfish induced avoidance; again, this effect was reversed by injection with chlordiazepoxide. Our results demonstrate that crayfish exhibit a form of anxiety similar to that described in vertebrates, suggesting the conservation of several underlying mechanisms during evolution. Analyses of this ancestral behavior in a simple model reveal a new route to understanding anxiety and may alter our conceptions of the emotional status of invertebrates.

Remembering Stressful Events Situations surrounding emotional events are better remembered than others that accompany neutral events. However, in severe pathological states such as posttraumatic stress disorder (PTSD), exposure to threatening situations can also result in memory impairment. In this case, a hypermnesia for a salient trauma-related cue is associated with loss of memory for important aspects of the traumatic event. The memory for the core traumatic event is enhanced, but the capacity to place it in the right place and in response to the right cues is reduced. Kaouane et al. (p. 1510 , published online 23 February) associated a high-intensity threat with the infusion of corticosterone in the hippocampus to induce PTSD-like memory impairments in mice. The animals became unable to identify the threat context as the right predictor of the threat, and they showed a fear response for discrete salient cues normally identified as safe. The neural activation patterns in the amygdala and hippocampal regions of these mice were similar to those observed in human PTSD.

Insomnia, the most prevalent sleep disorder worldwide, confers marked risks for both physical and mental health. Furthermore, insomnia is associated with considerable direct and indirect healthcare costs. Recent guidelines in the US and Europe unequivocally conclude that cognitive behavioural therapy for insomnia (CBT-I) should be the first-line treatment for the disorder. Current treatment approaches are in stark contrast to these clear recommendations, not least across Europe, where, if any treatment at all is delivered, hypnotic medication still is the dominant therapeutic modality. To address this situation, a Task Force of the European Sleep Research Society and the European Insomnia Network met in May 2018. The Task Force proposed establishing a European CBT-I Academy that would enable a Europe-wide system of standardized CBT-I training and training centre accreditation. This article summarizes the deliberations of the Task Force concerning definition and ingredients of CBT-I, preconditions for health professionals to teach CBT-I, the way in which CBT-I should be taught, who should be taught CBT-I and to whom CBT-I should be administered. Furthermore, diverse aspects of CBT-I care and delivery were discussed and incorporated into a stepped-care model for insomnia.

The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [(11)C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.

In tomographic medical imaging (PET, SPECT, CT), differences in data acquisition and organization are a major hurdle for the development of tomographic reconstruction software. The implementation of a given reconstruction algorithm is usually limited to a specific set of conditions, depending on the modality, the purpose of the study, the input data, or on the characteristics of the reconstruction algorithm itself. It causes restricted or limited use of algorithms, differences in implementation, code duplication, impractical code development, and difficulties for comparing different methods. This work attempts to address these issues by proposing a unified and generic code framework for formatting, processing and reconstructing acquired multi-modal and multi-dimensional data. The proposed iterative framework processes in the same way elements from list-mode (i.e. events) and histogrammed (i.e. sinogram or other bins) data sets. Each element is processed separately, which opens the way for highly parallel execution. A unique iterative algorithm engine makes use of generic core components corresponding to the main parts of the reconstruction process. Features that are specific to different modalities and algorithms are embedded into specific components inheriting from the generic abstract components. Temporal dimensions are taken into account in the core architecture. The framework is implemented in an open-source C++ parallel platform, called CASToR (customizable and advanced software for tomographic reconstruction). Performance assessments show that the time loss due to genericity remains acceptable, being one order of magnitude slower compared to a manufacturer's software optimized for computational efficiency for a given system geometry. Specific optimizations were made possible by the underlying data set organization and processing and allowed for an average speed-up factor ranging from 1.54 to 3.07 when compared to more conventional implementations. Using parallel programming, an almost linear speed-up increase (factor of 0.85 times number of cores) was obtained in a realistic clinical PET setting. In conclusion, the proposed framework offers a substantial flexibility for the integration of new reconstruction algorithms while maintaining computation efficiency.

The absolute requirement for reproduction implies that the hypothalamo-pituitary-gonadal axis, controlling fertility, is an evolutionary robust mechanism. The GnRH neurons of the hypothalamus represent the key cell type within the body dictating fertility. However, the level of functional redundancy within the GnRH neuron population is unknown. As a result of a fortuitous transgene insertion event, GNR23 mice exhibit a marked allele-dependent reduction in GnRH neuron number within their brain. Wild-type mice have approximately 600 GnRH neurons, compared with approximately 200 (34%) and approximately 70 (12%) in GNR23(+/-) and GNR23(-/-) mice, respectively. Using these mice, we examined the minimal GnRH neuron requirements for fertility. Male GNR23(-/-) mice exhibited normal fertility. In contrast, female GNR23(-/-) mice were markedly subfertile, failing to produce normal litters, have estrous cycles, or ovulate. The failure of ovulation resulted from an inability of the few existing GnRH neurons to generate the LH surge. This was not the case, however, for the first cycle at puberty that appeared normal. Together, these observations demonstrate that 12% of the GnRH neuron population is sufficient for pulsatile gonadotropin secretion and puberty onset, whereas between 12 and 34% are required for cyclical control in adult female mice. This indicates that substantial redundancy exists within the GnRH neuronal population and suggests that the great majority of GnRH neurons must be dysfunctional before fertility is affected.

The intestine is a key organ for lipid uptake and distribution, and abnormal intestinal lipid metabolism is associated with obesity and hyperlipidemia. Although multiple regulatory gut hormones secreted from enteroendocrine cells (EEs) regulate systemic lipid homeostasis, such as appetite control and energy balance in adipose tissue, their respective roles regarding lipid metabolism in the intestine are not well understood. We demonstrate that tachykinins (TKs), one of the most abundant secreted peptides expressed in midgut EEs, regulate intestinal lipid production and subsequently control systemic lipid homeostasis in Drosophila and that TKs repress lipogenesis in enterocytes (ECs) associated with TKR99D receptor and protein kinase A (PKA) signaling. Interestingly, nutrient deprivation enhances the production of TKs in the midgut. Finally, unlike the physiological roles of TKs produced from the brain, gut-derived TKs do not affect behavior, thus demonstrating that gut TK hormones specifically regulate intestinal lipid metabolism without affecting neuronal functions.

Adolescence is a crucial developmental period characterized by specific behaviors reflecting the immaturity of decision-making abilities. However, the maturation of precise cognitive processes and their neurobiological correlates at this period remain poorly understood. Here, we investigate whether a differential developmental time course of dopamine (DA) pathways during late adolescence could explain the emergence of particular executive and motivational components of goal-directed behavior. First, using a contingency degradation protocol, we demonstrate that adolescent rats display a specific deficit when the causal relationship between their actions and their consequences is changed. When the rats become adults, this deficit disappears. In contrast, actions of adolescents remain sensitive to outcome devaluation or to the influence of a pavlovian-conditioned stimulus. This aspect of cognitive maturation parallels a delayed development of the DA system, especially the mesocortical pathway involved in action adaptation to rule changes. Unlike in striatal and nucleus accumbens regions, DA fibers and DA tissue content continue to increase in the medial prefrontal cortex from juvenile to adult age. Moreover, a sustained overexpression of DA receptors is observed in the prefrontal region until the end of adolescence. These findings highlight the relationship between the emergence of specific cognitive processes, in particular the adaptation to changes in action consequences, and the delayed maturation of the mesocortical DA pathway. Similar developmental processes in humans could contribute to the adolescent vulnerability to the emergence of several psychiatric disorders characterized by decision-making deficits.

The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications.

Brain imaging studies have shown that slow and progressive cerebral atrophy characterized the development of Alzheimer's Disease (AD). Despite a large number of studies dedicated to AD, key questions about the lifespan evolution of AD biomarkers remain open. When does the AD model diverge from the normal aging model? What is the lifespan trajectory of imaging biomarkers for AD? How do the trajectories of biomarkers in AD differ from normal aging? To answer these questions, we proposed an innovative way by inferring brain structure model across the entire lifespan using a massive number of MRI (N = 4329). We compared the normal model based on 2944 control subjects with the pathological model based on 3262 patients (AD + Mild cognitive Impaired subjects) older than 55 years and controls younger than 55 years. Our study provides evidences of early divergence of the AD models from the normal aging trajectory before 40 years for the hippocampus, followed by the lateral ventricles and the amygdala around 40 years. Moreover, our lifespan model reveals the evolution of these biomarkers and suggests close abnormality evolution for the hippocampus and the amygdala, whereas trajectory of ventricular enlargement appears to follow an inverted U-shape. Finally, our models indicate that medial temporal lobe atrophy and ventricular enlargement are two mid-life physiopathological events characterizing AD brain.

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Deep brain stimulation (DBS) is a reversible technique that is currently used for the treatment of Parkinson disease and may be suitable for the treatment of psychiatric disorders. Whether DBS inactivates the target structure is still a matter of debate. Here, from findings obtained in rats, we propose DBS of the subthalamic nucleus (STN) as a possible treatment for cocaine addiction to be further tested in human studies. We show that STN DBS reversibly reduces the motivation to work for an i.v. injection of cocaine, and it increases motivation to work for sucrose pellets. These opposite effects may result from STN DBS effect on the positive affective properties of these rewards. Indeed, we further show that STN DBS reduces the preference for a place previously associated with the rewarding properties of cocaine, and it increases the preference for a place associated with food. Because these findings are consistent with those observed after STN lesions [Baunez C, Dias C, Cador M, Amalric M (2005) Nat Neurosci 8:484-489], they suggest that STN DBS mimics an inactivation of the STN on motivational processes. Furthermore, given that one of the major challenges for cocaine addiction is to find a treatment that reduces the craving for the drug without diminishing the motivation for naturally rewarding activities, our findings validate STN as a good target and DBS as the appropriate technique for a promising therapeutic strategy in the treatment of cocaine addiction.