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Nat Commun ; 10(1): 1455, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926783

RESUMO

The ventral tegmental area (VTA) is a heterogeneous midbrain structure, containing neurons and astrocytes, that coordinates behaviors by integrating activity from numerous afferents. Within neuron-astrocyte networks, astrocytes control signals from distinct afferents in a circuit-specific manner, but whether this capacity scales up to drive motivated behavior has been undetermined. Using genetic and optical dissection strategies we report that VTA astrocytes tune glutamatergic signaling selectively on local inhibitory neurons to drive a functional circuit for learned avoidance. In this circuit, astrocytes facilitate excitation of VTA GABA neurons to increase inhibition of dopamine neurons, eliciting real-time and learned avoidance behavior that is sufficient to impede expression of preference for reward. Loss of one glutamate transporter (GLT-1) from VTA astrocytes selectively blocks these avoidance behaviors and spares preference for reward. Thus, VTA astrocytes selectively regulate excitation of local GABA neurons to drive a distinct avoidance circuit that opposes approach behavior.


Assuntos
Astrócitos/fisiologia , Aprendizagem da Esquiva/fisiologia , Comportamento de Escolha/fisiologia , Área Tegmentar Ventral/citologia , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Feminino , Neurônios GABAérgicos/fisiologia , Ácido Glutâmico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Inibição Neural
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