The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Elife
; 52016 05 13.
Article
em En
| MEDLINE
| ID: mdl-27177420
ABSTRACT
Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing 'leak' current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual mouse SNr neurons. We discovered that SNr neurons express the sodium leak channel, NALCN, and that SNr neurons lacking NALCN have impaired spontaneous firing. In addition, NALCN is involved in the modulation of excitability by changes in glycolysis and by activation of muscarinic acetylcholine receptors. Our findings suggest that disruption of NALCN could impair the basal ganglia circuit, which may underlie the severe motor deficits in humans carrying mutations in NALCN.
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Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
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Neurônios GABAérgicos
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Parte Reticular da Substância Negra
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Glicólise
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Canais Iônicos
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos