Only watching others making their experiences is insufficient to enhance adult neurogenesis and water maze performance in mice

In the context of television consumption and its opportunity costs the question arises how far experiencing mere representations of the outer world would have the same neural and cognitive consequences than actively interacting with that environment. Here we demonstrate that physical interaction and direct exposition are essential for the beneficial effects of environmental enrichment. In our experiment, the mice living in a simple standard cage placed in the centre of a large enriched environment only indirectly experiencing the stimulus-rich surroundings (IND) did not display increased adult hippocampal neurogenesis. In contrast, the mice living in and directly experiencing the surrounding enriched environment (DIR) and mice living in a similar enriched cage containing an uninhabited inner cage (ENR) showed enhanced neurogenesis compared to mice in control conditions (CTR). Similarly, the beneficial effects of environmental enrichment on learning performance in the Morris Water maze depended on the direct interaction of the individual with the enrichment. In contrast, indirectly experiencing a stimulus-rich environment failed to improve memory functions indicating that direct interaction and activity within the stimulus-rich environment are necessary to induce structural and functional changes in the hippocampus

Why and How Physical Activity Promotes Experience-Induced Brain Plasticity

Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses) are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, increasing the likelihood of cognitive challenges. In the wild (other than in front of a TV), no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading “an active life” but an evolutionarily fundamental aspect of “activity,” which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback

Recurrent stress across life may improve cognitive performance in individual rats, suggesting the induction of resilience

Depressive symptoms are often accompanied by cognitive impairments and recurrent depressive episodes are discussed as a potential risk for dementia. Especially, stressful life events are considered a potent risk factor for depression. Here, we induced recurrent stress-induced depressive episodes over the life span of rats, followed by cognitive assessment in the symptom-free period. Rats exposed to stress-induced depressive episodes learned faster than control rats. A high degree of stress-induced depressive-like behavior early in the paradigm was a predictor of improved cognitive performance, suggesting induction of resilience. Subsequently, exposure to lorazepam prior to stress-induced depressive episodes and cognitive testing in a nonaversive environment prevented the positive effect. This indicates a beneficial effect of the stress-associated situation, with the existence of individual coping abilities. Altogether, stress may in some have a beneficial effect, yet for those individuals unable to tackle these aversive events, consecutive unpleasant episodes may lead to worse cognitive performance later in life

A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

BACKGROUND AND PURPOSE: Obesity and associated co‐morbidities, such as type 2 diabetes and non‐alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co‐morbidities. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP‐089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight‐independent effects of KBP‐089 using a weight‐matched group. KEY RESULTS: Rats fed a high‐fat diet were treated, s.c., with KBP‐089 0.625, 1.25, 2.5 μg·kg(−1) or vehicle. KB‐089 induced in a dose‐dependent and sustained weight loss (~17% by 2.5 μg·kg(−1)). Moreover, KBP‐089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP‐089 improved glucose homeostasis through improved insulin action. To obtain a weight‐matched group, significantly less food was offered (9% less than in the KBP‐089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP‐089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP‐089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. CONCLUSIONS AND IMPLICATIONS: The novel DACRA, KBP‐089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet‐induced weight loss

Adult-Generated Hippocampal Neurons Allow the Flexible Use of Spatially Precise Learning Strategies

Despite enormous progress in the past few years the specific contribution of newly born granule cells to the function of the adult hippocampus is still not clear. We hypothesized that in order to solve this question particular attention has to be paid to the specific design, the analysis, and the interpretation of the learning test to be used. We thus designed a behavioral experiment along hypotheses derived from a computational model predicting that new neurons might be particularly relevant for learning conditions, in which novel aspects arise in familiar situations, thus putting high demands on the qualitative aspects of (re-)learning

Genetic contributions to two special factors of neuroticism are associated with affluence, higher intelligence, better health, and longer life

Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of neuroticism as a whole. A recent study showed that a 12-item neuroticism scale described one broad trait of general neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general neuroticism lived shorter lives, individuals whose neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of neuroticism—anxiety/tension and worry/vulnerability—and how they contrast with that of general neuroticism. First, we show that, whereas the polygenic load for neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of neuroticism. Finally, we show that different neurological pathways are linked to each of these neuroticism phenotypes.</p

A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence

Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach—multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)—to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination—as well as genes expressed in the synapse, and those involved in the regulation of the nervous system—may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.</p

Biological Earth observation with animal sensors

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

Functional relevance of adult neurogenesis in the murine hippocampus

Im Gyrus dentatus (dentate gyrus, DG) des Hippokampus (HC) entstehen auch im Erwachsenenalter fortwährend neue Neurone, welche sich zu funktionsfähigen Körnerzellen differenzieren und in die bestehenden Schaltkreise funktional integrieren. Zwischen der Anzahl adult generierter Körnerzellen und der Leistungsfähigkeit in der Akquisitionsphase hippokampusabhängiger Verhaltenstests besteht eine positive Korrelation . Die spezifische funktionale Relevanz adult generierter Neurone im Kontext hippokampaler Informationsprozessierung ist jedoch nicht bekannt. Ein Modell nach legt eine Rolle des DG bei der Enkodierung für eine Speicherung in CA3 bestimmter Informationen nahe und postuliert die Notwendigkeit einer Adaptation des Enkodierungsmechanismus bei Veränderungen der Stimuluskonfigurationen in der Umwelt des jeweiligen Organismus. Im Zuge einer solchen Adaptation tritt das Problem einer katastrophalen Interferenz zwischen bereits erlernten und neuen Aktivitätsmustern im DG auf, welches im Modell durch das Hinzufügen neuer Neurone effektiv vermieden werden kann. Das Auftreten einer katastrophalen Interferenz im Kontext veränderlicher Stimuluskonfigurationen in der Umwelt bei gleichzeitiger Suppression adulter Neurogenese stellt eine Prädiktion der o.g. Hypothese dar und wurde in der vorliegenden Arbeit experimentell überprüft. Zur effektiven Suppression adulter Neurogenese konnte die systemische Applikation des Zytostatikums Temozolomid (TMZ) als Methode ohne das Auftreten negativer Nebenwirkungen erfolgreich etabliert werden. Als Paradigma zur Testung hippokampusabhängigen räumlichen Lernens diente die Morris Water Maze (MWM) unter Verwendung eines Umkehrlernprotokolls, wodurch auch die in der o.g. Hypothese enthaltene Veränderung relevanter Stimuluskonfigurationen berücksichtigt wurde. Hinsichtlich des allgemeinen physiologischen Zustands sowie der grundsätzlichen Fähigkeit die MWM zu erlernen, unterschieden sich Kontrollen und TMZ behandelte Tiere nicht voneinander. Erst nach dem Wechsel der Plattformposition wurde ein signifikanter Unterschied beobachtet: Unbehandelte Tiere adaptierten effektiv innerhalb weniger Versuche an die neue Situation, wohingegen die behandelten Tiere eine perseverierende Präferenz für die vorige Zielposition zeigten. Weitere Gruppenunterschiede traten hinsichtlich qualitativer Parameter des Akquisitionsprozesses auf. Die erhobenen Daten bestätigen somit die auf dem o.g. Modell beruhende Prädiktion, wonach die Möglichkeit eines flexiblen Umgangs mit einer sich hinsichtlich verhaltensrelevanter Stimuli verändernden Umwelt nach erfolgter Suppression adulter Neurogenese signifikant beeinträchtigt ist. Auf der Grundlage dieser Befunde wurde eine allgemeine Hypothese zur funktionalen Relevanz adulter Neurogenese entwickelt und erfolgreich zur Interpretation der Ergebnisse anderer Autoren und Testparadigmen verwendet, wodurch sich die gefundenen Effekte gut in die Vorstellung verschiedener, zum Zwecke des Lernens und Erinnerns interagierender Hirnareale einfügt.In the dentate gyrus (DG) of the hippocampus (HC) new neurons are born throughout adulthood. The new neurons differentiate into granule cells and become functionally integrated into the existing networks. Despite a clear positive correlation between the number of adult borne neurons and the animals abilities shown in the aquisition phase of hippocampus dependent learning tasks, the specific functional relevance of adult neurogenesis for information processing in the HC remains unknown . A model by suggests a role of the DG for the encoding of information to be stored in region CA3 and proposes the need for an adaptation of the encoding network in the context of changing environmental stimulus configurations. Intimately related to such an adaptation is the problem of catastrophic interference between old, already learned patterns of activity in the DG with new ones. As a consequence effective encoding of new activity patterns as well as retrieval of previously stored information becomes severely impaired. In the model adding new neurons through adult neurogenesis allow the network to avoid this problem by providing plasticity to the encoding mechanism. Therefore refering to that model the prediction can be derived that in mice with pharmacological ablated adult neurogenesis changes of behaviorally relevant, spatial stimulus configurations in the environment result in catastrophic interference. This prediction was tested experimentally in this study. To effectively suppress adult neurogenesis without confounding side effects the systemic application of the cytostatic drug Temozolomide (TMZ) was established. The animals spatial learning abilities were tested using the Morris water maze test paradigm (MWM) running a protocol including a reversal learning to cover the changing stimulus configurations mentioned in the hypothesis above. Regarding the common physiological state and the animals general ability to learn the MWM task no significant differences between controls TMZ treated mice were found. Significant differences appeared only after platform reversal: control mice adapt effectively to the new situation whereas the treated animals show a perseverating preference for the previous goal position. Mice with ablated adult neurogenesis need significantly more trials to adapt to the changed platform position. Furthermore specific differences regarding qualitative aspects of learning and effective compensation strategies were found during the acquisition phase of the MWM task. Therefore the results of this study strongly support the hypothesis that flexible adaptation to changes of behaviorally relevant stimulus configurations in the environment is significantly impaired in mice with suppressed adult neurogenesis. Finally a functional hypothesis is postulated and used to interpret the data from other authors fitting the observed effects nicely into the view of multiple interconnected brain areas facilitating learning and memory