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Cell Rep ; 32(11): 108156, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937133

RESUMO

Substantia nigra (SNc) dopaminergic neurons respond to aversive stimuli with inhibitory pauses in firing followed by transient rebound activation. We tested integration of inhibitory synaptic inputs onto SNc neurons from genetically defined populations in dorsal striatum (striosome and matrix) and external globus pallidus (GPe; parvalbumin- and Lhx6-positive), and examined their contribution to pause-rebound firing. Activation of striosome projections, which target "dendron bouquets" in the pars reticulata (SNr), consistently quiets firing and relief from striosome inhibition triggers rebound activity. Striosomal inhibitory postsynaptic currents (IPSCs) display a prominent GABA-B receptor-mediated component that strengthens the impact of SNr dendrite synapses on somatic excitability and enables rebounding. By contrast, GPe projections activate GABA-A receptors on the soma and proximal dendrites but do not result in rebounding. Lastly, optical mapping shows that dorsal striatum selectively inhibits the ventral population of SNc neurons, which are intrinsically capable of rebounding. Therefore, we define a distinct striatonigral circuit for generating dopamine rebound.


Assuntos
Gânglios da Base/fisiologia , Neurônios Dopaminérgicos/fisiologia , Inibição Neural/fisiologia , Substância Negra/fisiologia , Animais , Cálcio/metabolismo , Corpo Estriado/fisiologia , Dendritos/fisiologia , Dopamina/metabolismo , Feminino , Globo Pálido/fisiologia , Masculino , Camundongos , Modelos Neurológicos , Receptores de GABA-A/metabolismo , Receptores de GABA-B/metabolismo , Sinapses/metabolismo
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