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

Elife
Authors
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.

Year of Publication
2016
Journal
Elife
Volume
5
Date Published
2016 May 13
ISSN
2050-084X
URL
DOI
10.7554/eLife.15271
PubMed ID
27177420
PubMed Central ID
PMC4902561
Links
Grant list
DP1 EB016985 / EB / NIBIB NIH HHS / United States
F31 NS077633 / NS / NINDS NIH HHS / United States
P30 NS072030 / NS / NINDS NIH HHS / United States
R01 NS055031 / NS / NINDS NIH HHS / United States