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1.
Mol Psychiatry ; 25(2): 506, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31366917

RESUMO

A correction to this paper has been published and can be accessed via a link at the top of the paper.

2.
Mol Psychiatry ; 25(2): 491-505, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-29695836

RESUMO

The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.


Assuntos
Aprendizagem da Esquiva/fisiologia , Corpo Estriado/metabolismo , Neurônios/metabolismo , Animais , Transtornos de Ansiedade , Encéfalo/metabolismo , Linhagem Celular , Feminino , Substância Cinzenta/metabolismo , Hábitos , Inibição Psicológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Optogenética/métodos , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Transtorno de Movimento Estereotipado
3.
J Neurosci ; 38(14): 3547-3558, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29523623

RESUMO

The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity.SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and population calcium activity from the dorsal striatum during ad libitum feeding and an operant task that resulted in mice obtaining food pellets. Dorsal striatal neurons exhibited long ramps in activity that preceded actions by several seconds, and may reflect upcoming actions. Understanding how the striatum controls the preparation and generation of actions may lead to improved therapies for disorders, such as drug addiction or obesity.


Assuntos
Corpo Estriado/fisiologia , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Animais , Cálcio/metabolismo , Corpo Estriado/citologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Movimento , Neurônios/metabolismo , Neurônios/fisiologia , Recompensa
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