Behavioral Output Research Articles

Future avenues in Drosophila mushroom body research.

How does the brain translate sensory information into complex behaviors? With relatively small neuronal numbers, readable behavioral outputs, and an unparalleled genetic toolkit, the Drosophila mushroom body (MB) offers an excellent model to address this question in the context of associative learning and memory. Recent technological breakthroughs, such as the freshly completed full-brain connectome, multiomics approaches, CRISPR-mediated gene editing, and machine learning techniques, led to major advancements in our understanding of the MB circuit at the molecular, structural, physiological, and functional levels. Despite significant progress in individual MB areas, the field still faces the fundamental challenge of resolving how these different levels combine and interact to ultimately control the behavior of an individual fly. In this review, we discuss various aspects of MB research, with a focus on the current knowledge gaps, and an outlook on the future methodological developments required to reach an overall view of the neurobiological basis of learning and memory.

Current Output Estimation of 12 Volts Solar Power Line Source Using Fuzzy Logic-Based Modelling Technique

This study used the fuzzy logic-based system to estimate the output current of a solar panel system at specified amount of power and percentage of cloud cover in the atmosphere. This established the fuzzy rule-based system which was applied from a research study to analyze the behavior of the current output wherein the available solar panels are three 100 watts and two 50 watts making it difficult to measure the current with power of 175 watts and 350 watts. The amount of the produced current was established through the fuzzy rule-based system stated as the following: if the power is low and the atmosphere is almost cloudy then the current produced is very small; if the power is high and the atmosphere is cloudy then the current produced is small; if the power is medium and the atmosphere is partially cloudy then the current produced is average; if the power is high and the atmosphere is clear then the current produced is large. Through defuzzification the fuzzy system was implemented by computing the output value using the centroid method.

Single cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity

The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of ‘Ghost’ neurons endowed with atypical molecular and functional identity. Compared to ‘classical’ Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are ‘invisible’ to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.

Dark Side of the Career: Reflections from an Online Discussion Platform

Career counseling research has neglected how workplace experiences affect employees’ careers. Therefore, this study aimed to understand the employees’ feelings and thoughts regarding their working life. Accordingly, this study adopted a qualitative approach and investigated 1928 posts by using Thematic Analysis from an online discussion platform. The research data were the entries of the platform under the title of "working life" from 2000 to 2022. These entries were analyzed by using MAXQDA software. Results showed three clusters: The naïve cluster comprised expectations and skills from the beginning of working life. In naïve cluster, users expressed how different their expectations in working life from reality. The black box cluster included workplace deviance and poor working conditions. In this cluster, users especially expressed problems about interpersonal relationships in the working environment. Finally, the cost cluster comprised physical, emotional, behavioral, and spiritual outputs of working life. In these outputs, users revealed their burnout, insecurity, and unhappiness. The findings were discussed from the psychology of working theory perspective, and related literature.

Istradefylline/L‐DOPA Parkinson's disease therapy and energy coupling

AbstractBackgroundBoth dopamine and adenosine are physiologically involved in cellular energy metabolism.AimNovel approaches targeting delaying progression strategies for Parkinson's disease (PD) examined the effects of long‐term use of A2AR antagonist/istradefylline (IST) adjunct to L‐DOPA (LD), nutshell IST‐LD, with an expected energy coupling (EC) to attenuate neuronal excitotoxicity.MethodsA single‐center prospective open cohort study was conducted at the Department of Neurology, Okinawa Islands, Japan. The cohort included incident and prevalent PD cases that were non‐randomly assigned to the IST‐LD (n = 90) and LD (n = 157) groups, followed by an open‐label treatment in clinical practice from October 2013 to September 2020. Patients were evaluated using physician‐rated MDS‐UPDRS I/III, and patient‐rated MDS‐NMS using the total score, body weight, and blood biomarkers of EC.ResultsAs the primary clinical outcome, MDS‐UPDRS part III scores showed less worsening in the IST‐LD than in the LD group (1.29 ± 6.0 vs. 5.0 ± 6.5, p < 0.01) and off‐time Hoehn and Yahr stage (0.05 ± 0.49 vs. 0.26 ± 0.54, p < 0.01). As the secondary clinical outcome, the detected mean body weight losses were similar between the two groups; however, the evident linkage of the daily dose of LD and variations in the blood markers of IGF‐I and HKII, which were inferred as LD‐mediated energy demand effects, were partially attenuated by IST.ConclusionIST‐LD plays an essential role in behavioral outputs for patients with PD and might contribute to the interplay of energy‐consuming demands of LD with the attenuation of weight loss and emerging type 2 diabetes mellitus.

H hybrid control and MRD in a steel frame building subjected to excessive vibrations caused by the dynamic action of wind and earthquake

The dynamic loads from earthquakes and winds can destroy lives, cause collapse in civil structures, and interrupt basic services provided to the population. In this scenario, structural designs must be developed to decrease the damage induced by these actions. The objective of this work is to design a hybrid controller based on the H¥ optimization via state feedback and the magneto-rheological damper (MRD) to mitigate the excessive vibrations of a three-story steel frame building, represented through the shear building model, subjected to the simultaneous dynamic action of wind and earthquake. All research is based on computational simulation, experimental research and results will not be addressed. In the numerical analysis, digital computer and MATLAB® software are used, and implemented codes generate the expected results based on the mathematical modeling. With the application of the H¥ control technique via state feedback, the displacements were reduced by 77%. With MRD this reduction was 79%. With the hybrid controller, this reduction was 100%. Thus, the verifications in relation to maximum displacements were met for NBR 15421:2006, NBR 8800:2008 and NBR 6118:2014. From the results, it is concluded that the hybrid controller proved to be more efficient and achieved the proposed objective. The exogenous inputs had zero influence on the behavior of the system output.

Chronic exposure to gestodene impairs reproductive system in adult female zebrafish (Daniarerio)

Gestodene (GES) is widely used in human therapy and animal husbandry and is frequently detected in aquatic environments. Although GES adversely affects aquatic organisms at trace levels, its effects on the reproductive biology of fish remain inconclusive. In this study, female zebrafish (Danio rerio) were exposed to environmentally relevant levels of GES for the evaluation of the effects of GES on the reproductive system by using endpoints including gene expression, plasma steroid concentrations, histological and morphological analyses, copulatory behavior, and reproductive output. Adult female zebrafish exposed to environmentally relevant concentrations of GES (4.0, 40.2, and 372.7 ng/L) for 60 d demonstrated stagnant ovarian oocyte development, evidenced by an increase in the percentage of perinuclear and atretic oocytes and a decrease in the percentage of late vitellogenic oocytes. GES-exposed females were less attractive to males and had lower copulatory intimacy than females in control. Consequently, spawning (44.3–49.2 %) and egg fertilization rates (27.9–32.0 %) were decreased. The decreased survival of fertilized eggs and hatching rates were accompanied by increased malformations. These negative effects were associated with abnormal transcriptional levels of gonadal steroid hormones, which were regulated by genes (Hsd17β3, Hsd11β2, Hsd20β, Cyp19a1a, and Cyp11b). Overall, our findings suggest that GES impairs the reproductive system of zebrafish, which may threaten population stability.

Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology.

Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned and ingrained as habits, which can be evolutionarily advantageous as they reduce cognitive load and the expenditure of attentional resources. Repetitive behaviors can also be conscious and deliberate, and may occur in the absence of habit formation, typically when they are a feature of normal development in children, or neuropsychiatric disorders. They can be considered pathological when they interfere with social relationships and daily activities. For instance, people affected by obsessive-compulsive disorder, autism spectrum disorder, Huntington's disease and Gilles de la Tourette syndrome can display a wide range of symptoms like compulsive, stereotyped and ritualistic behaviors. The striatum nucleus of the basal ganglia is proposed to act as a master regulator of these repetitive behaviors through its circuit connections with sensorimotor, associative, and limbic areas of the cortex. However, the precise mechanisms within the striatum, detailing its compartmental organization, cellular specificity, and the intricacies of its downstream connections, remain an area of active research. In this review, we summarize evidence across multiple scales, including circuit-level, cellular, and molecular dimensions, to elucidate the striatal mechanisms underpinning repetitive behaviors and offer perspectives on the implicated disorders. We consider the close relationship between behavioral output and transcriptional changes, and thereby structural and circuit alterations, including those occurring through epigenetic processes.

Active Ankle–Foot Orthosis Design and Computer Simulation with Multi-Objective Parameter Optimization

There are many current active orthosis designs to assist with disabilities related to foot-drop, with most of them intervening during the whole gait cycle. We propose that, for the treatment of foot-drop, it is possible to design an ankle–foot device that will assist a walking user only during the dorsiflexion stages of the gait, avoiding interference with other stages, by using a single actuator with a simple transmission and a suspension block. This design can be improved by the use of multi-objective optimization to obtain a static set of parameters that are applicable to varying initial conditions. We present a computer simulation study of an active ankle–foot orthosis design, based on the interaction of a cam and lever with a suspension block, with the objective of assisting only with dorsiflexion during the gait cycle, leaving the rest of the movements unimpeded while reducing the complexity and weight of the device. This design is validated using a full simulation environment that includes the movements of the lower leg and foot, as they interact with our device and a ground element. As part of the design and validation, we found sets of mechanical and control parameters that provoke adequate output behavior of the orthosis to help the wearer perform a moderate-speed, normal gait. To optimize the design, we proposed three objectives to warrant ankle angle accuracy, minimal oscillations, and low energy consumption. A set of solutions was obtained with multi-objective optimization algorithms NSGA-II and RVEA to tune the parameters of the active orthosis. The solutions set from RVEA resulted in lower mean and standard deviation values for the oscillations and energy objectives in comparison to the solutions from NSGA-II, while for the MSE objective, NSGA-II obtained lower mean and standard deviation; for the energy consumption objective, the mean score using RVEA is 17% less than with NSGA-II. The orthosis is shown to be robust to differences in initial ankle angles. We observed that it is possible to obtain a broad set of solutions with a good performance during the gait cycle in controlled spaces and that in this application, the RVEA algorithm results in a better option for optimization to balance the objectives.

Pupillary Responses Reflect Dynamic Changes in Multiple Cognitive Factors During Associative Learning in Primates.

Associative learning involves complex interactions of multiple cognitive factors. While adult subjects can articulate these factors verbally, for model animals such as macaques, we rely on behavioral outputs. In our study, we used pupillary responses as an alternative measure to capture these underlying cognitive changes. We recorded the dynamic changes in the pupils of three male macaques when they learned the associations between visual stimuli and reward sizes under the classical Pavlovian experimental paradigm. We found that during the long-term learning process, the gradual changes in the pupillary response reflect the changes in the cognitive state of the animals. The pupillary response can be explained by a linear combination of components corresponding to multiple cognitive factors. These components reflect the impact of visual stimuli on the pupils, the prediction of reward values associated with the visual stimuli, and the macaques' understanding of the current experimental reward rules. The changing patterns of these factors during interday and intraday learning clearly demonstrate the enhancement of current reward-stimulus association and the weakening of previous reward-stimulus association. Our study shows that the dynamic response of pupils can serve as an objective indicator to characterize the psychological changes of animals, understand their learning process, and provide important tools for exploring animal behavior during the learning process.

Angiotensin II involvement in the development and persistence of amphetamine-induced sensitization: Striatal dopamine reuptake implications.

Amphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1-R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1-R role in the development and maintenance of AMPH-induced sensitization. Also, the AT1-R involvement in striatal dopamine reuptake was analysed. The sensitization protocol consisted of daily AMPH administration for 5days and tested 21 days after withdrawal. An AT1-R antagonist, candesartan, was administered before or after AMPH exposure to evaluate the participation of AT1-R in the development and maintenance of sensitization, respectively. Sensitization was evaluated by locomotor activity and c-Fos immunostaining. Changes in dopamine reuptake kinetics were evaluated 1day after AT1-R blockade withdrawal treatment, with or without the addition of AMPH in vitro. The social interaction test was performed as another behavioural output. Repeated AMPH exposure induced behavioural and neurochemical sensitization, which was prevented and reversed by candesartan. The AT1-R blockade increased the dopamine reuptake kinetics. Neither the AMPH administration nor the AT1-R blockade altered the performance of social interaction. Our results highlight the AT1-R's crucial role in AMPH sensitization. The enhancement of dopamine reuptake kinetics induced by the AT1-R blockade might attenuate the neuroadaptive changes that lead to AMPH sensitization and its self-perpetuation. Therefore, AT1-R is a prominent candidate as a target for pharmacological treatment of pathologies related to dopamine imbalance, including drug addiction and schizophrenia.

Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin

Structural neuroplasticity (changes in the size, strength, number, and targets of synaptic connections) can be modified by sleep and sleep disruption. However, the causal relationships between genetic perturbations, sleep loss, neuroplasticity, and behavior remain unclear. The C.elegans GABAergic DVB neuron undergoes structural plasticity in adult males in response to adolescent stress, which rewires synaptic connections, alters behavior, and is dependent on conserved autism-associated genes NRXN1/nrx-1 and NLGN3/nlg-1. We find that four methods of sleep deprivation transiently induce DVB neurite extension in day 1 adults and increase the time to spicule protraction, which is the functional and behavioral output of the DVB neuron. Loss of nrx-1 and nlg-1 prevent DVB structural plasticity and behavioral changes at day 1 caused by adolescent sleep loss. Therefore, nrx-1 and nlg-1 mediate the morphologic and behavioral consequences of sleep loss, providing insight into the relationship between sleep, neuroplasticity, behavior, and neurologic disease.

Experience-Dependent Remodeling of Juvenile Brain Olfactory Sensory Neuron Synaptic Connectivity in an Early-Life Critical Period.

Early-life olfactory sensory experience induces dramatic synaptic glomeruli remodeling in the Drosophila juvenile brain, which is experientially dose-dependent, temporally restricted, and transiently reversible only in a short, well-defined critical period. The directionality of brain circuit synaptic connectivity remodeling is determined by the specific odorant acting on the respondent receptor class of olfactory sensory neurons. In general, each neuron class expresses only a single odorant receptor and innervates a single olfactory synaptic glomerulus. In the Drosophila genetic model, the full array of olfactory glomeruli has been precisely mapped by odorant responsiveness and behavioral output. Ethyl butyrate (EB) odorant activates Or42a receptor neurons innervating the VM7 glomerulus. During the early-life critical period, EB experience drives dose-dependent synapse elimination in the Or42a olfactory sensory neurons. Timed periods of dosed EB odorant exposure allow investigation of experience-dependent circuit connectivity pruning in juvenile brain. Confocal microscopy imaging of antennal lobe synaptic glomeruli is done with Or42a receptor-driven transgenic markers that provide quantification of synapse number and innervation volume. The sophisticated Drosophila genetic toolkit enables the systematic dissection of the cellular and molecular mechanisms mediating brain circuit remodeling.

Risk-averse bi-level planning model for maximizing renewable energy hosting capacity via empowering seasonal hydrogen storage

Renewables (i.e., solar and wind power) in the Nordic area have highly seasonal characteristics, which severely restrict the wide development of renewables since they can be excessive in summer but insufficient in winter with intermittent outputs. The conventional battery energy storage system (BESS) with short-term adjustment functionality cannot eliminate the seasonal imbalance of renewables. In this regard, a risk-based bi-level planning model is presented to maximize the hosting capacity (HC) of renewables through configuring seasonal hydrogen storage (SHS) and BESS. Specifically, the upper level applies a multi-objective scheme to maximize HC and minimize the investment cost simultaneously. In turn, the lower level is driven by maximizing the profits of the distribution system operator (DSO) with the implementation of price-based demand response (PBDR). Due to forecasting errors of renewables and load resulting from intermittent output and random behaviors, a stochastic programming (SP) method is developed to address and adapt multiple uncertain fluctuations. Moreover, the conditional value-at-risk (CVaR) is introduced to measure the effect of the risks raised by multiple uncertainties on system operation. Finally, numerical studies are employed to verify the effectiveness of the proposed model. Compared to the cases without considering PBDR and SHS, the total renewable energy HC in the proposed model is increased by 2.30 MW and 0.37 MW, respectively, while the yearly cost benefit of DSO is enhanced by 28063.2 US$ and 17823.7 US$, respectively. The promising results demonstrate the empowerment of SHS can promote the cross-seasonal consumption of renewables, effectively maximizing the HC and improving the economic operation of distribution systems.

PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome

Fragile X Syndrome (FXS) is the most prevalent monogenetic form of intellectual disability and autism. Recently, dysregulation of insulin signaling (IS) and aberrations in mitochondrial function have emerged as robust, evolutionarily conserved components of FXS pathophysiology. However, the mechanisms by which altered IS and mitochondrial dysfunction impact behavior in the context of FXS remain elusive. Here, we show that normalization of IS improves mitochondrial volume and function in flies that lack expression of dfmr1, the Drosophila homolog of the causal gene of FXS in humans. Further, we demonstrate that dysregulation of IS underlies diminished expression of the mitochondrial master regulator PGC-1α/Spargel in dfmr1 mutant flies. These results are behaviorally relevant, as we show that pan-neuronal augmentation of PGC-1α/Spargel improves circadian behavior in dfmr1 mutants. Notably, we also show that modulation of PGC-1α/Spargel expression in wild-type flies phenocopies the dfmr1 mutant circadian defect. Taken together, the results presented herein provide a mechanistic link between mitochondrial function and circadian behavior both in FXS pathogenesis as well as more broadly at the interface between metabolism and behavioral output.

Reward contingency gates selective cholinergic suppression of amygdala neurons.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward - even prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex. Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling, while also facilitating firing in BLA GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Reward contingency gates selective cholinergic suppression of amygdala neurons

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex. Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling, while also facilitating firing in BLA GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Circuit formation and sensory perception in the mouse olfactory system.

In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of glomeruli is genetically determined, the glomerular structure is plastic and can be modified by environmental stimuli. If the pups are exposed to a particular odorant, responding glomeruli become larger recruiting the dendrites of connecting projection neurons and interneurons. This imprinting not only increases the sensitivity to the exposed odor, but also imposes the positive quality on imprinted memory. External odor information represented as an odor map in the OB is transmitted to the olfactory cortex (OC) and amygdala for decision making to elicit emotional and behavioral outputs using two distinct neural pathways, innate and learned. Innate olfactory circuits start to work right after birth, whereas learned circuits become functional later on. In this paper, the recent progress will be summarized in the study of olfactory circuit formation and odor perception in mice. We will also propose new hypotheses on the timing and gating of olfactory circuit activity in relation to the respiration cycle.

An application of systems thinking to group‐based organisations

AbstractThis study conceptualised self‐help groups (SHGs) from the behavioural systems perspective. It adopted the grounded theory approach for data collection and analysis; and the development of structural frameworks through causal inferences. The behavioural system of the SHGs had psychological and behavioural input (interest, motivation, intention, value, belief and need), psychological and behavioural process (adaptability, receptibility and cognitive ability), psychological and behavioural output (social behaviour, psychological behaviour, economical behaviour and ecological behaviour), and environment (macroeconomic environment, policy environment, social–cultural–political environment of village, and institutional environment of the village). The psychological and behavioural input, process, and output exhibited interdependencies. The conceptual categories within them showed causal interactions. The study provided a new lens to the debate on self‐help group‐based microentrepreneurship and group dynamics. The study found the systemic approach of SHG functioning and the peer pressure mechanisms built upon psychological and behavioural characteristics.

The Kinematics of Proal Chewing in Rats.

Chewing kinematics are well-documented in several mammal species with fused mandibular symphyses, but relatively understudied in mammals with an unfused symphysis, despite the fact that more than half of extant Mammalia have an unfused mandibular symphysis. The Wistar brown rat (Rattus norvegicus) is widely used in human health research, including studies of mastication or neurological studies where mastication is the output behavior. These animals are known to have unfused mandibular symphyses and proal jaw (rostrocaudal) motion during occlusion, but the lack of high resolution, 3-dimensional analysis of rat chewing leaves the functional significance of symphyseal mobility unknown. We used biplanar fluoroscopy and the X-ray reconstruction of moving morphology workflow to quantify chewing kinematics in 3 brown rats, quantifying overall jaw kinematics, including motions about the temporomandibular joint and unfused mandibular symphysis. During occlusion, the teeth and the mandibular condyle translate almost exclusively anteriorly (proal) during occlusion, with little motion in any other degrees of freedom. At the symphysis, we observed minimal flexion throughout the chew cycle. Overall, there are fundamental differences in jaw kinematics between rats and other mammals and therefore rats are not an appropriate proxy for ancestral mammal jaw mechanics. Additionally, differences between humans and rat chewing kinematics must be considered when using rats as a clinical model for pathological feeding research.