Neurons for hunger and thirst transmit a negative-valence teaching signal
TL;DR: It is found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal, and these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-Valence signals during restoration of homeostasis.
Abstract: Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.
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TL;DR: A primer on DREADDs is provided highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.
1,145 citations
TL;DR: This open-source population-based optimization technique called Hunger Games Search is designed to be a standard tool for optimization in different areas of artificial intelligence and machine learning with several new exploratory and exploitative features, high performance, and high optimization capacity.
Abstract: A recent set of overused population-based methods have been published in recent years. Despite their popularity, most of them have uncertain, immature performance, partially done verifications, similar overused metaphors, similar immature exploration and exploitation components and operations, and an insecure tradeoff between exploration and exploitation trends in most of the new real-world cases. Therefore, all users need to extensively modify and adjust their operations based on main evolutionary methods to reach faster convergence, more stable balance, and high-quality results. To move the optimization community one step ahead toward more focus on performance rather than change of metaphor, a general-purpose population-based optimization technique called Hunger Games Search (HGS) is proposed in this research with a simple structure, special stability features and very competitive performance to realize the solutions of both constrained and unconstrained problems more effectively. The proposed HGS is designed according to the hunger-driven activities and behavioural choice of animals. This dynamic, fitness-wise search method follows a simple concept of “Hunger” as the most crucial homeostatic motivation and reason for behaviours, decisions, and actions in the life of all animals to make the process of optimization more understandable and consistent for new users and decision-makers. The Hunger Games Search incorporates the concept of hunger into the feature process; in other words, an adaptive weight based on the concept of hunger is designed and employed to simulate the effect of hunger on each search step. It follows the computationally logical rules (games) utilized by almost all animals and these rival activities and games are often adaptive evolutionary by securing higher chances of survival and food acquisition. This method's main feature is its dynamic nature, simple structure, and high performance in terms of convergence and acceptable quality of solutions, proving to be more efficient than the current optimization methods. The effectiveness of HGS was verified by comparing HGS with a comprehensive set of popular and advanced algorithms on 23 well-known optimization functions and the IEEE CEC 2014 benchmark test suite. Also, the HGS was applied to several engineering problems to demonstrate its applicability. The results validate the effectiveness of the proposed optimizer compared to popular essential optimizers, several advanced variants of the existing methods, and several CEC winners and powerful differential evolution (DE)-based methods abbreviated as LSHADE, SPS_L_SHADE_EIG, LSHADE_cnEpSi, SHADE, SADE, MPEDE, and JDE methods in handling many single-objective problems. We designed this open-source population-based method to be a standard tool for optimization in different areas of artificial intelligence and machine learning with several new exploratory and exploitative features, high performance, and high optimization capacity. The method is very flexible and scalable to be extended to fit more form of optimization cases in both structural aspects and application sides. This paper's source codes, supplementary files, Latex and office source files, sources of plots, a brief version and pseudocode, and an open-source software toolkit for solving optimization problems with Hunger Games Search and online web service for any question, feedback, suggestion, and idea on HGS algorithm will be available to the public at https://aliasgharheidari.com/HGS.html .
529 citations
TL;DR: This review describes and assess different classes of fluorescent protein indicators of neural activity and focuses on how indicator characteristics relate to their use in living animals and on likely areas of future progress.
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528 citations
TL;DR: The findings establish the vagal gut-to-brain axis as an integral component of the neuronal reward pathway and suggest novel vagal stimulation approaches to affective disorders.
443 citations
Cites background from "Neurons for hunger and thirst trans..."
..., 2016) while conveying negative valence (Betley et al., 2015)....
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...Consistently, activating the hypothalamic AgRP-positive ‘‘drive’’ neurons counteract parabrachium-mediated satiety (Campos et al., 2016) while conveying negative valence (Betley et al., 2015)....
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TL;DR: The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences.
Abstract: Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences.
416 citations
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TL;DR: A family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo are developed and provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
Abstract: Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
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TL;DR: The evidence from interaction studies shows the strong mediating control of instrumental responses by Pavlovian conditioning procedures, and demonstrates the surprising power of Pavlosian concepts in predicting the outcomes of many kinds of interaction experiments.
Abstract: The history of 2-process learning theory is described, and the logical and empirical validity of its major postulates is examined. The assumption of 2 acquisition processes requires the demonstration of an empirical interaction between 2 types of reinforcement contingencies and (a) response classes, (b) reinforcing stimulus classes, or (c) characteristics of the learned behavior itself. The mediation postulates of 2-process theory which argue that CRs are intimately involved in the control of instrumental responding are emphasized, and 2 major lines of evidence that stem uniquely from these postulates are examined : (a) the concurrent development and maintenance of instrumental responses and conditioned reflexes, and (b) the interaction between separately conducted Pavlovian conditioning contingencies and instrumental training contingencies in the control of instrumental behavior. The evidence from concurrent measurement studies provides, at the very best, only weak support for the mediational hypotheses of 2-process theory. In contrast, the evidence from interaction studies shows the strong mediating control of instrumental responses by Pavlovian conditioning procedures, and demonstrates the surprising power of Pavlovian concepts in predicting the outcomes of many kinds of interaction experiments.
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