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The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.

Elife. 2016 May 13;5. doi:10.7554/eLife.15271
Andrew Lutas 1 , Carolina Lahmann 1 , Magali Soumillon 2 , Gary Yellen 1
Andrew Lutas 1 , Carolina Lahmann 1 , Magali Soumillon 2 , Gary Yellen 1

[No authors listed]

Author information
  • 1 Department of Neurobiology, Harvard Medical School, Boston, United States.
  • 2 Broad Institute, Cambridge, United States.
全文

摘要


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.

KEYWORDS: basal ganglia, leak current, metabolism and excitability, mouse, neuroscience, spontaneous firing

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
agebarcode1barcode2cell typegfpsource namestraintissuetissue subtype
Sample 11
Mus musculus GSM2072087: Sample 11; Mus musculus; RNA-Seq RNA-Seq NextSeq 500 postnatal day 15 AAGAGGCA CGCGTCTT GFP-positive GABAergic SNr neurons GFP positive postnatal day 15_GFP positive C57BL/6 brain Substantia nigra pars reticulata (SNr)
Sample 10
Mus musculus GSM2072086: Sample 10; Mus musculus; RNA-Seq RNA-Seq NextSeq 500 postnatal day 15 CGAGGCTG CGCGTCTT GFP-positive GABAergic SNr neurons GFP positive postnatal day 15_GFP positive C57BL/6 brain Substantia nigra pars reticulata (SNr)
Sample 8
Mus musculus GSM2072085: Sample 8; Mus musculus; RNA-Seq RNA-Seq NextSeq 500 postnatal day 15 CAGAGAGG CGCGTCTT GFP-positive GABAergic SNr neurons GFP positive postnatal day 15_GFP positive C57BL/6 brain Substantia nigra pars reticulata (SNr)
Sample 7
Mus musculus GSM2072084: Sample 7; Mus musculus; RNA-Seq RNA-Seq NextSeq 500 postnatal day 15 CTCTCTAC CGCGTCTT GFP-positive GABAergic SNr neurons GFP positive postnatal day 15_GFP positive C57BL/6 brain Substantia nigra pars reticulata (SNr)
Sample 6
Mus musculus GSM2072083: Sample 6; Mus musculus; RNA-Seq RNA-Seq NextSeq 500 postnatal day 15 TAGGCATG CGCGTCTT GFP-positive GABAergic SNr neurons GFP positive postnatal day 15_GFP positive C57BL/6 brain Substantia nigra pars reticulata (SNr)