A cell type-specific cortico-subcortical brain circuit for investigatory and novelty-seeking behavior

INTRODUCTION: Motivational drives are internal states that can be different even in similar interactions with external stimuli. Curiosity as the motivational drive for novelty-seeking and investigating the surrounding environment is for survival as essential and intrinsic as hunger. Curiosity, hunger, and appetitive aggression drive three different goal-directed behaviors—novelty seeking, food eating, and hunting—but these behaviors are composed of similar actions in animals. This similarity of actions has made it challenging to study novelty seeking and distinguish it from eating and hunting in nonarticulating animals. The brain mechanisms underlying this basic survival drive, curiosity, and novelty-seeking behavior have remained unclear. RATIONALE: In spite of having well-developed techniques to study mouse brain circuits, there are many controversial and different results in the field of motivational behavior. This has left the functions of motivational brain regions such as the zona incerta (ZI) still uncertain. Not having a transparent, nonreinforced, and easily replicable paradigm is one of the main causes of this uncertainty. Therefore, we chose a simple solution to conduct our research: giving the mouse freedom to choose what it wants—double free-access choice. By examining mice in an experimental battery of object free-access double-choice (FADC) and social interaction tests—using optogenetics, chemogenetics, calcium fiber photometry, multichannel recording electrophysiology, and multicolor mRNA in situ hybridization—we uncovered a cell type–specific cortico-subcortical brain circuit of the curiosity and novelty-seeking behavior. RESULTS: We analyzed the transitions within action sequences in object FADC and social interaction tests. Frequency and hidden Markov model analyses showed that mice choose different action sequences in interaction with novel objects and in early periods of interaction with novel conspecifics compared with interaction with familiar objects or later periods of interaction with conspecifics, which we categorized as deep and shallow investigation, respectively. This finding helped us to define a measure of depth of investigation that indicates how much a mouse prefers deep over shallow investigation and reflects the mouse’s motivational level to investigate, regardless of total duration of investigation. Optogenetic activation of inhibitory neurons in medial ZI (ZIm), ZImGAD2 neurons, showed a dramatic increase in positive arousal level, depth of investigation, and duration of interaction with conspecifics and novel objects compared with familiar objects, crickets, and food. Optogenetic or chemogenetic deactivation of these neurons decreased depth and duration of investigation. Moreover, we found that ZImGAD2 neurons are more active during deep investigation as compared with during shallow investigation. We found that activation of prelimbic cortex (PL) axons into ZIm increases arousal level, and chemogenetic deactivation of these axons decreases the duration and depth of investigation. Calcium fiber photometry of these axons showed no difference in activity between shallow and deep investigation, suggesting a nonspecific motivation. Optogenetic activation of ZImGAD2 axons into lateral periaqueductal gray (lPAG) increases the arousal level, whereas chemogenetic deactivation of these axons decreases duration and depth of investigation. Calcium fiber photometry of these axons showed high activity during deep investigation and no significant activity during shallow investigation, suggesting a thresholding mechanism. Last, we found a new subpopulation of inhibitory neurons in ZIm expressing tachykinin 1 (TAC1) that monosynaptically receive PL inputs and project to lPAG. Optogenetic activation and deactivation of these neurons, respectively, increased and decreased depth and duration of investigation. CONCLUSION: Our experiments revealed different action sequences based on the motivational level of novelty seeking. Moreover, we uncovered a new brain circuit underlying curiosity and novelty-seeking behavior, connecting excitatory neurons of PL to lPAG through TAC1+ inhibitory neurons of ZIm

Perception of Symmetries in Drawings of Graphs

Symmetry is an important factor in human perception in general, as well as in the visualization of graphs in particular. There are three main types of symmetry: reflective, translational, and rotational. We report the results of a human subjects experiment to determine what types of symmetries are more salient in drawings of graphs. We found statistically significant evidence that vertical reflective symmetry is the most dominant (when selecting among vertical reflective, horizontal reflective, and translational). We also found statistically significant evidence that rotational symmetry is affected by the number of radial axes (the more, the better), with a notable exception at four axes.Comment: Appears in the Proceedings of the 26th International Symposium on Graph Drawing and Network Visualization (GD 2018

Nano-Tubular Cellulose for Bioprocess Technology Development

Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC) justifies its suitability for use in “cold pasteurization” processes and its promoting activity in bioprocessing (fermentation). The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator). Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc

Adoptive T-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy

Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches

Predictors of 1-year compliance with adaptive servoventilation in patients with heart failure and sleep disordered breathing: preliminary data from the ADVENT-HF trial

Despite its effectiveness in suppressing sleep disordered breathing (SDB), positive airway pressure therapy (PAP) is not always well tolerated by patients and long-term adherence can be problematic. Recently, two multicentre, randomised clinical trials (RCTs) tested the effects of PAP for patients with cardiovascular disease and co-existing SDB on morbidity and mortality with negative outcomes [1, 2]. Relatively poor adherence to PAP therapy (mean 3.7 and 3.3 h·day-1, respectively) in these two trials might have contributed to their poor results. Indeed, higher PAP use per day is associated with better clinical outcomes than lower use [3]

The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol

[EN] Introduction Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%¿12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults. Method The My Active and Healthy Aging (My-AHA) consortium has developed an information and communications technology¿based platform to support active and healthy aging through early detection of prefrailty and provision of individually tailored interventions, targeting multidomain risks for frailty across physical activity, cognitive activity, diet and nutrition, sleep, and psychosocial activities. Six hundred adults aged 60 years and older will be recruited to participate in a multinational, multisite 18-month randomized controlled trial to test the efficacy of the My-AHA platform to detect prefrailty and the efficacy of individually tailored interventions to prevent development of clinical frailty in this cohort. A total of 10 centers from Italy, Germany, Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and Australia will participate in the randomized controlled trial. Results Pilot testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been completed with a small group of older adults in Europe with the full randomized controlled trial scheduled to commence in 2018. Discussion The My-AHA study will expand the understanding of antecedent risk factors for clinical frailty so as to deliver targeted interventions to adults with prefrailty. Through the use of an information and communications technology platform that can connect with multiple devices within the older adult's own home, the My-AHA platform is designed to measure an individual's risk factors for frailty across multiple domains and then deliver personalized domain-specific interventions to the individual. The My-AHA platform is technology-agnostic, enabling the integration of new devices and sensor platforms as they emerge.This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 689582 and the Australian National Health and Medical Research Council (NHRMC) European Union grant scheme (1115818). M.J.S. reports personal fees from Eli Lilly (Australia) Pty Ltd and grants from Novotech Pty Ltd, outside the submitted work. All other authors report nothing to disclose.Summers, MJ.; Rainero, I.; Vercelli, AE.; Aumayr, GA.; De Rosario Martínez, H.; Mönter, M.; Kawashima, R. (2018). 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The replication database: documenting the replicability of psychological science

In psychological science, replicability — repeating a study with a new sample achieving consistent results (Parsons et al., 2022) — is critical for affirming the validity of scientific findings. Despite its importance, replication efforts are few and far between in psychological science with many attempts failing to corroborate past findings. This scarcity, compounded by the difficulty in accessing replication data, jeopardizes the efficient allocation of research resources and impedes scientific advancement. Addressing this crucial gap, we present the Replication Database (https://forrt-replications.shinyapps.io/fred_explorer), a novel platform hosting 1,239 original findings paired with replication findings. The infrastructure of this database allows researchers to submit, access, and engage with replication findings. The database makes replications visible, easily findable via a graphical user interface, and tracks replication rates across various factors, such as publication year or journal. This will facilitate future efforts to evaluate the robustness of psychological research