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1.
Sensors (Basel) ; 24(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38894277

RESUMO

If we visit famous and iconic landmarks, we may want to take a photo of them. However, such sites are usually crowded, and taking photos with only landmarks without people could be challenging. This paper aims to automatically remove people in a picture and produce a natural image of the landmark alone. To this end, it presents Thanos, a system to generate authentic human-removed images in crowded places. It is designed to produce high-quality images with reasonable computation cost using short video clips of a few seconds. For this purpose, a multi-frame-based recovery region minimization method is proposed. The key idea is to aggregate information partially available from multiple image frames to minimize the area to be restored. The evaluation result presents that the proposed method outperforms alternatives; it shows lower Fréchet Inception Distance (FID) scores with comparable processing latency. It is also shown that the images by Thanos achieve a lower FID score than those of existing applications; Thanos's score is 242.8, while those by Retouch-photos and Samsung object eraser are 249.4 and 271.2, respectively.

2.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 4843-4849, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38265902

RESUMO

This paper studies a new curve-fitting approach to data on Riemannian manifolds. We define a principal curve based on a mixture model for observations and unobserved latent variables and propose a new algorithm to estimate the principal curve for given data points on Riemannian manifolds.

3.
J Neurosci ; 44(5)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38123360

RESUMO

Mutations in the activity-dependent transcription factor MEF2C have been associated with several neuropsychiatric disorders. Among these, autism spectrum disorder (ASD)-related behavioral deficits are manifested. Multiple animal models that harbor mutations in Mef2c have provided compelling evidence that Mef2c is indeed an ASD gene. However, studies in mice with germline or global brain knock-out of Mef2c are limited in their ability to identify the precise neural substrates and cell types that are required for the expression of Mef2c-mediated ASD behaviors. Given the role of hippocampal neurogenesis in cognitive and social behaviors, in this study we aimed to investigate the role of Mef2c in the structure and function of newly generated dentate granule cells (DGCs) in the postnatal hippocampus and to determine whether disrupted Mef2c function is responsible for manifesting ASD behaviors. Overexpression of Mef2c (Mef2cOE ) arrested the transition of neurogenesis at progenitor stages, as indicated by sustained expression of Sox2+ in Mef2cOE DGCs. Conditional knock-out of Mef2c (Mef2ccko ) allowed neuronal commitment of Mef2ccko cells; however, Mef2ccko impaired not only dendritic arborization and spine formation but also synaptic transmission onto Mef2ccko DGCs. Moreover, the abnormal structure and function of Mef2ccko DGCs led to deficits in social interaction and social novelty recognition, which are key characteristics of ASD behaviors. Thus, our study revealed a dose-dependent requirement of Mef2c in the control of distinct steps of neurogenesis, as well as a critical cell-autonomous function of Mef2c in newborn DGCs in the expression of proper social behavior in both sexes.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Feminino , Camundongos , Animais , Transtorno do Espectro Autista/genética , Hipocampo , Neurônios/fisiologia , Neurogênese/fisiologia , Fatores de Transcrição MEF2/genética
4.
Nat Commun ; 14(1): 4085, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438336

RESUMO

The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to the dorsal striatum, which regulates goal-directed and habitual seeking. However, the role of GPe arky neurons in reward-seeking remains unknown. Here, we identified that a majority of arky neurons target the dorsolateral striatum (DLS). Using fiber photometry, we found that arky activities were higher during random interval (RI; habit) compared to random ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated that arky neuron activities have sufficient information to distinguish between RR and RI behavior. Genetic ablation of this arkyGPe→DLS circuit facilitated a shift from goal-directed to habitual behavior. Conversely, chemogenetic activation globally reduced seeking behaviors, which was blocked by systemic D1R agonism. Our findings reveal a role of this arkyGPe→DLS circuit in constraining habitual seeking in male mice, which is relevant to addictive behaviors and other compulsive disorders.


Assuntos
Corpo Estriado , Globo Pálido , Masculino , Animais , Camundongos , Hábitos , Gânglios da Base , Neostriado
5.
Sci Adv ; 9(24): eadh9239, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37327345

RESUMO

An imbalance in goal-directed and habitual behavioral control is a hallmark of decision-making-related disorders, including addiction. Although external globus pallidus (GPe) is critical for action selection, which harbors enriched astrocytes, the role of GPe astrocytes involved in action-selection strategies remained unknown. Using in vivo calcium signaling with fiber photometry, we found substantially attenuated GPe astrocytic activity during habitual learning compared to goal-directed learning. The support vector machine analysis predicted the behavioral outcomes. Chemogenetic activation of the astrocytes or inhibition of GPe pan-neuronal activities facilitates the transition from habit to goal-directed reward-seeking behavior. Next, we found increased astrocyte-specific GABA (γ-aminobutyric acid) transporter type 3 (GAT3) messenger RNA expression during habit learning. Notably, the pharmacological inhibition of GAT3 occluded astrocyte activation-induced transition from habitual to goal-directed behavior. On the other hand, attentional stimuli shifted the habit to goal-directed behaviors. Our findings suggest that the GPe astrocytes regulate the action selection strategy and behavioral flexibility.


Assuntos
Astrócitos , Globo Pálido , Globo Pálido/fisiologia , Neurônios/fisiologia , Aprendizagem/fisiologia , Recompensa
6.
Curr Psychol ; : 1-12, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37359591

RESUMO

This study examines adolescent game usage and corresponding health-related risk behaviors during a period of limited social interaction and activity due to the COVID-19 pandemic. Participants included 225 middle- and 225 high-school students in Seoul who completed a survey online from October 1 to 30, 2021. The study measured participants' game usage level and the health-related risk behavior index. Findings showed that participants who engaged in excessive gaming showed higher levels of health-related risk behaviors. A multivariate analysis of variance was conducted to compare the health-related risk behaviors of students in the general, potential, and high-risk groups on excessive gaming. Results indicated that female students in the high-risk group showed higher stress levels and fatigue (f = 5.549, p < .01, Cohen's d = 0.016) than the males of the same group. However, male students showed higher physical inactivity levels (f = 3.195, p > .05, Cohen's d = 0.009) than females. The post hoc test indicated clear sex distinctions among the general, potential, and high-risk groups on excessive gaming (p < .001). Among the high-risk game usage group, female students displayed a higher level of risk behaviors than males. Adolescent gaming addiction should be considered an emotional and behavioral disorder for which parental guidance and support are needed, and counseling experts and professionals must come together to provide a cure and reform program.

7.
Front Public Health ; 11: 1093541, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923028

RESUMO

Introduction: New conflict types have arisen in leisure sports activities due to social regulations designed to address COVID-19. We analyze the differences in conflict-inducing factors and coping strategies across various types of leisure sports and levels of spatial proximity. Methods: Korean adults aged between 20 and 60 years, who had participated in leisure sports activities since the COVID-19 outbreak in January 2020, were surveyed, and 508 responses were collected for analysis. The differences in leisure sports conflicts and coping strategies across the types of leisure sports participation and spatial proximity were tested. Results: The results show that conflict due to prejudice was higher in typical indoor sports activities, such as Pilates, yoga, and gym workouts, whereas conflict due to competition or not observing etiquette was higher in indoor golf. Second, conflict due to prior expectations and prejudice was high in outdoor sports activities, such as jogging and hiking. Finally, all participants showed avoidance behavior, but it was observed more frequently in outdoor sports than indoor sports. Discussion: The study reveals how much leisure conflict is induced by various types of leisure sports participation, particularly during outdoor activities, which usually feature a relatively low density of participants. It underscores the necessity of developing structural approaches to resolving leisure conflicts in dangerous spaces or requiring intensive management and creating new leisure sports activities.


Assuntos
COVID-19 , Esportes , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Pandemias , COVID-19/epidemiologia , Atividades de Lazer , Adaptação Psicológica
8.
Malar J ; 22(1): 41, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737724

RESUMO

BACKGROUND: The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported. Although it is crucial to systematically understand the main causes of the disruption to malaria control and synthesize strategies to prepare for future pandemics, such studies are scarce. Therefore, this study aims to better identify barriers against and strategies for malaria control. METHODS: Following the PRISMA guidelines and through searches of electronic databases and Google Scholar, a systematic literature review was conducted to identify studies pertaining to malaria control published between January 2020 and December 2021. Only studies that discussed reported barriers and/or strategies related to malaria were included for the review. The Mixed Methods Quality Appraisal Tool (MMAT) and the Authority, Accuracy, Coverage, Objectivity, Date and Significance (AACODS) checklist were used for quality appraisal. Key information such as literature type, study design, setting and population, interventions, outcomes, barriers, and strategies were extracted. With an existing framework of four dimensions (accessibility, affordability, availability, and acceptability) further subdivided by the supply and demand sides, this study synthesized information on barriers and strategies related to malaria control and further categorized the strategies based on the time frame. RESULTS: From the 30 selected studies, 27 barriers and 39 strategies were identified. The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control. The strategies were distinguished between short-term, for instant response, and mid to long-term for future readiness. CONCLUSIONS: The pandemic resulted in complex barriers to malaria control, particularly imposing a double burden on LMICs. Identifying strategies to overcome said barriers provides useful insights in the decision-making processes for the current and future pandemic. Cross-cutting strategies that integrate all dimensions need to be considered. Health system strengthening and resilience strategy appropriate for country-specific context is fundamental.


Assuntos
COVID-19 , Malária , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Países em Desenvolvimento , Controle de Doenças Transmissíveis , Malária/epidemiologia , Malária/prevenção & controle
9.
Front Public Health ; 11: 1229571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259785

RESUMO

Introduction: This study examines how job market changes affect individuals' leisure choices and satisfaction, focusing on worker classes that have undergone daily life changes (e.g., economic and social activities) due to the coronavirus disease-2019 (COVID-19) pandemic. Methods: A population-based cross-sectional study design was employed. South Korean workers aged 20-59 years answered an online survey administered from September 14 to October 4, 2021. Ultimately, 764 responses were used in the analysis. The measures used in this study consisted of factors affecting infectious disease risk perception and leisure satisfaction among the six new worker classes that emerged during the pandemic, according to socio-demographic status. Results: The results showed that among male participants, social, emotional, physical, environmental, and educational factors of leisure satisfaction were more strongly affected, with higher social, physical, and interpersonal relationships being factors in the perception of infectious disease risk. Among female participants, the interpersonal relationship factor of perceived risk was significantly affected by the social, emotional, and educational factors of leisure satisfaction. Interpersonal relationships, affected leisure satisfaction among members of Classes 1-3, who experienced no change in pay. However, for the members of Class6 who experienced a decrease in pay, the economic factor negatively affected leisure satisfaction and played a pivotal role in our findings. Conclusion: This study verified the risk factors that inhibit leisure satisfaction among new worker classes that emerged during the COVID-19 pandemic. Furthermore, the psychological health of people suffering pandemic-related financial constraints was affected, as they experienced a lower quality of life owing to reduced leisure activities and satisfaction.


Assuntos
COVID-19 , Doenças Transmissíveis , Feminino , Humanos , Masculino , COVID-19/epidemiologia , Estudos Transversais , Atividades de Lazer , Pandemias , Qualidade de Vida , Adulto Jovem , Adulto , Pessoa de Meia-Idade
10.
Neuropharmacology ; 198: 108759, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34433087

RESUMO

In the striatum, two main types of GABAergic medium spiny neurons (MSNs), denoted striatonigral (or direct-pathway MSNs, dMSNs) and striatopallidal neurons (indirect-pathway MSNs, iMSNs), form circuits with distinct pallidal nuclei, which sends "GO" or "NO-GO" signals through the thalamus. These striatopallidal circuits evaluate and execute reward-seeking and taking behaviors. Especially, the dorsal striatum can be further divided into the dorsomedial striatum (DMS, equivalent to caudate in primates and humans) and dorsolateral striatum (DLS, equivalent to putamen), which orchestrates goal-directed and habitual reward-seeking and taking behaviors, respectively. Using optogenetics, chemogenetics and in vivo calcium imaging technologies combined with electrophysiology and digitalized behavior phenotyping, recent studies have revealed cell-, circuit- and context-specific functions of these microcircuits in addictive behaviors. Also, region-specific astrocytes regulate the homeostatic activities of the dMSNs and iMSNs as well as the downstream circuits, which determine the net balance of cortico-striato-pallidal activities to the thalamic neurons. This review will summarize the recent progress of striatopallidal circuits focusing on astrocyte-neuron interaction and, reward- and alcohol-seeking behaviors. Our review will also discuss the translational and clinical implications of these microcircuit studies. This article is part of the special Issue on "Neurocircuitry Modulating Drug and Alcohol Abuse".


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Astrócitos/fisiologia , Comportamento de Procura de Droga/fisiologia , Etanol , Globo Pálido/fisiologia , Neostriado/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Animais , Condicionamento Operante , Humanos , Recompensa
11.
Artigo em Inglês | MEDLINE | ID: mdl-33406754

RESUMO

An increasing trend among employees has been to engage in leisure activities, which has been proven to be an effective method of overcoming work stress. As a result, employees are doing "Other Things" (i.e., non-work activities) as a way to relieve stress. Based on the existing studies on rumination, this study considered doing "Other Things" as a new concept of "leisure rumination" and identified its influence as a means to help employees recover from work stress. Accordingly, this study provided basic data on the meaning of leisure activities and leisure rumination in office workers who suffer from failure to recover from work stress using partial least squares structural equation modeling. This study was conducted on employees residing in the Seoul metropolitan area and the Gyeongsang-do district in November 2019 through a structured questionnaire. The results of this study verified the significance of leisure rumination and the possibility of it being utilized as a practical research tool for leisure activities. Our findings may be considered when planning interventions for work addiction and burnout through leisure rumination.


Assuntos
Atividades de Lazer , Estresse Ocupacional , Teoria Psicológica , Ruminação Cognitiva , Humanos , Intenção , Estresse Ocupacional/epidemiologia , Seul , Inquéritos e Questionários
12.
Artigo em Inglês | MEDLINE | ID: mdl-33430042

RESUMO

This study aimed to investigate the difference in people's perceived crowding and risk perception during leisure activities using the criteria of spatial proximity during the COVID-19 pandemic. COVID-19 is a viral respiratory tract disease that poses an increasing risk of infection through person-to-person transmission in a confined space or close proximity to an infected person. It is thus crucial to maintain a sufficiently safe distance from others during leisure activities. In this study, measures concerning leisure activity spaces and the current status of leisure activities were investigated. Data were gathered from a total of 1078 participants via an online survey conducted from 26 to 29 October 2020. Frequency analysis was performed to investigate the sample characteristics and exploratory factor analysis was performed to analyze the validity of the measurement tools. Results revealed that people's perceived crowding of leisure activity spaces directly influenced their participation in leisure activities. Regarding age, those in their 20s were more aware of congestion and their risk perception was higher than those in their 40s and 50s. It was found that people perceived cultural and artistic activities to be dangerous as they often take place as part of tourism and leisure activities and amidst crowds. However, their high-risk perception indirectly influenced their participation patterns, making it difficult to enjoy leisure activities. To lower the risk perception of leisure activity spaces, it was necessary to secure more safe distancing than current regulations require. Future research must conduct a longitudinal investigation by objectively stratifying the degree of perceived crowding.


Assuntos
COVID-19 , Aglomeração , Atividades de Lazer , Pandemias , Adulto , Humanos , Pessoa de Meia-Idade , Distanciamento Físico , Medição de Risco , Inquéritos e Questionários , Adulto Jovem
14.
FASEB J ; 35(2): e21227, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33247500

RESUMO

Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane-bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport chain, can lead to a variety of disorders. Recognized conditions with such mutations include Leigh syndrome and hereditary tumors such as pheochromocytoma and paraganglioma (PPGL), renal cell carcinoma, and gastrointestinal stromal tumor. Tumors appear in SDH mutation carriers with dominant inheritance due to loss of heterozygosity in susceptible cells. Here, we describe a mouse model intended to reproduce hereditary PPGL through Cre-mediated loss of SDHC in cells that express tyrosine hydroxylase (TH), a compartment where PPGL is known to originate. We report that while there is modest expansion of TH+ glomus cells in the carotid body upon SDHC loss, PPGL is not observed in such mice, even in the presence of a conditional dominant negative p53 protein and chronic hypoxia. Instead, we report an unexpected phenotype of nondiabetic obesity beginning at about 20 weeks of age. We hypothesize that this obesity is caused by TH+ cell loss or altered phenotype in key compartments of the central nervous system responsible for regulating feeding behavior, coupled with metabolic changes due to loss of peripheral catecholamine production.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Modelos Animais de Doenças , Síndromes Neoplásicas Hereditárias/genética , Obesidade/genética , Fenótipo , Feocromocitoma/genética , Succinato Desidrogenase/genética , Neoplasias das Glândulas Suprarrenais/patologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndromes Neoplásicas Hereditárias/patologia , Obesidade/patologia , Feocromocitoma/patologia , Succinato Desidrogenase/deficiência
15.
J Neurochem ; 156(2): 212-224, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32594517

RESUMO

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model. We hypothesize that Pv-FSI activation elicits changes in cortical glutamate levels and reward-seeking behaviors. To determine molecular and behavioral effects of Pv-FSI, we performed microdialysis and operant conditioning tasks for sucrose and alcohol rewards. In addition, we also examined how alcohol reward itself affects Pv-FSI functioning. Interestingly, our microdialysis results demonstrate that alcohol exposure inhibits Pv-FSI functioning in the medial prefrontal cortex (mPFC) and this consequently can regulate glutamate levels downstream in the nucleus accumbens. For sucrose reward-seeking behaviors, Pv-FSI activation in the mPFC increases sucrose self-administration whereas it does not promote alcohol seeking. For alcohol rewards, however, Pv-FSI activation in the mPFC results in increased compulsive head entry in operant chambers during devaluation procedures. Overall, our results suggest that not only do Pv-FSI contribute to changes in the cortical microcircuit and reward-seeking behaviors but also that alcohol affects Pv-FSI neurotransmission. Therefore, Pv-FSI has prompted interest in their role in maintaining a balance in neuronal excitation/inhibition and in regulating reward-seeking processes such as compulsivity, all of which are important factors for excessive alcohol seeking.


Assuntos
Comportamento Animal/fisiologia , Interneurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Recompensa , Alcoolismo/metabolismo , Animais , Condicionamento Operante , Etanol/farmacologia , Masculino , Camundongos , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Parvalbuminas/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Sacarose/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-33096689

RESUMO

This study utilizes the Theory of Planned Behavior (TPB) variables-including "attitude," "subjective norms," and "perceived behavioral control"-to understand the relationship between mask-wearing behavior and physical/non-physical leisure activity participation in Koreans as well as the tendencies behind mask-wearing intentions within leisure activities. The measurement tools used attitude, subjective norms, control, and mask use intention factors based on the TPB. Overall, 545 individuals participated, and the non-overlapping regions, sex, and age were considered through the stratified sampling method. The survey was conducted online owing to COVID-19, and collected data were derived through descriptive and multiple linear regression analyses. First, a difference in mask-wearing intention based on physical and non-physical leisure activities was identified; second, attitudes and perceived behaviors were considered in light of the dangers posed by COVID-19. It was found that control influences the tendency of intention to wear a mask depending on whether the group was engaged in physical or non-physical activity. Therefore, it can be stated that mask-wearing must be mandatory during physical and non-physical activities owing to respiratory diseases such as COVID-19. It is also important to simultaneously promote a positive attitude toward mask-wearing to enable people to believe that they can stay in full control of their own health.


Assuntos
Infecções por Coronavirus/prevenção & controle , Atividades de Lazer , Máscaras/tendências , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Humanos , Teoria Psicológica , República da Coreia , SARS-CoV-2
17.
Artigo em Inglês | MEDLINE | ID: mdl-32781702

RESUMO

This study aimed to create new classifications for occupations that have emerged from the COVID-19 pandemic in Korea, based on Reich's classifications for the United States. We examined Korean workers' occupational calling, psychological health, and quality of life. An online questionnaire was administered and data from 1029 Korean workers were analyzed. The questionnaire comprised the Korean version of the Multidimensional Calling Measure to assess occupational calling, the Psychosocial Well-being Index-short form for psychological health, and the Control, Autonomy, Self-realization, and Pleasure (CASP-19) scale for quality of life. We created a Korean-adapted version of the classes of occupation based on those created by the COVID-19 situation in the USA. Our results showed that Korean workers had a high perceived calling to work, and different classes showed different levels of quality of life and psychological health. We need a health concentration management system for essential groups or personal safety protection equipment should be provided. Education on infection control should be offered and effective medical system processes should be in place. We need to develop technology to respond to medical needs online, remotely, or telephonically. The government should implement policies to ensure job security and to improve wages and welfare.


Assuntos
Infecções por Coronavirus/epidemiologia , Saúde Mental , Ocupações/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Qualidade de Vida/psicologia , Betacoronavirus , COVID-19 , Humanos , Controle de Infecções/organização & administração , Masculino , Pandemias , Equipamento de Proteção Individual/provisão & distribuição , República da Coreia/epidemiologia , SARS-CoV-2 , Inquéritos e Questionários
18.
Biol Psychiatry ; 88(10): 797-808, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32564901

RESUMO

BACKGROUND: Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift. METHODS: To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors. RESULTS: The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition. CONCLUSIONS: Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior.


Assuntos
Astrócitos , Objetivos , Animais , Corpo Estriado , Camundongos , Neostriado , Recompensa
19.
Lab Anim Res ; 36: 9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322555

RESUMO

Psychiatric disorders are a prevalent global health problem, over 900 million individuals affected by a continuum of mental and substance use disorders. Due to this high prevalence, and the substantial direct and indirect societal costs, it is essential to understand the underlying mechanisms of these disorders to facilitate development of new and more effective treatments. Since the advent of recombinant DNA technologies in the early 1980s, genetically modified rodent models have significantly contributed to the genetic and molecular basis of psychiatric disorders. Despite significant advancements, many challenges remain after unsuccessful drug development based on rodent models. Recent human genetics show the polygenetic nature of mental disorders, identifying hundreds of allelic variants that confer increased risk. However, given the complexity of the brain, with many unique cell types, gene expression profiles, and developmental trajectories, proper animal models are needed more than ever to dissect genes and circuits in a cell type-specific manner to advance our understanding and treatment of psychiatric disorders. In this mini-review, we highlight current challenges and promises of using rodent models in advancing science and drug development, focusing on advanced techniques, and their applications to rodent models of psychiatric disorders.

20.
Addict Biol ; 25(3): e12754, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31012186

RESUMO

Waiting impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are vulnerable to alcohol abuse. However, it is not well understood whether chronic alcohol use increases the propensity for impulsive behavior. Here, we establish a novel experimental paradigm demonstrating that continuous binge-like ethanol exposure progressively leads to maladaptive impulsive behavior. To test waiting impulsivity, we employed the 5-choice serial reaction time task (5-CSRTT) in C57BL/6J male mice. We assessed premature responses in the fixed and variable intertrial interval (ITI) 5-CSRTT sessions. We further characterized our ethanol-induced impulsive mice using Open Field, y-maze, two-bottle choice, and an action-outcome task. Our results indicate that continuous binge-like ethanol exposure significantly increased premature responses when mice were tested in variable ITI sessions even during a prolonged abstinent period. Ethanol-induced impulsive mice exhibited anxiety-like behavior during chronic exposures. This behavior was also observed in a separate cohort that was subjected to 20 days of abstinence. Ethanol-treated mice were less motivated for a sucrose reward compared with air-exposed control mice, while also demonstrating reduced responding during action-outcome testing. Overall, ethanol-treated mice demonstrated increased impulsive behavior, but a reduced motivation for a sucrose reward. Although waiting impulsivity has been hypothesized to be a trait or risk factor for AUD, our findings indicate that maladaptive impulse control can also be potentiated or induced by continuous chronic ethanol exposure in mice.


Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Comportamento Impulsivo/efeitos dos fármacos , Animais , Ansiedade , Comportamento Animal/efeitos dos fármacos , Consumo Excessivo de Bebidas Alcoólicas , Comportamento de Escolha/efeitos dos fármacos , Masculino , Camundongos , Motivação/efeitos dos fármacos , Teste de Campo Aberto , Tempo de Reação/efeitos dos fármacos , Recompensa
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