Neuronal classification and marker gene identification via single-cell expression profiling of brainstem vestibular neurons subserving cerebellar learning.
Identification of marker genes expressed in specific cell types is essential for the genetic dissection of neural circuits. Here we report a new strategy for classifying heterogeneous populations of neurons into functionally distinct types and for identifying associated marker genes. Quantitative single-cell expression profiling of genes related to neurotransmitters and ion channels enables functional classification of neurons; transcript profiles for marker gene candidates identify molecular handles for manipulating each cell type. We apply this strategy to the mouse medial vestibular nucleus (MVN), which comprises several types of neurons subserving cerebellar-dependent learning in the vestibulo-ocular reflex. Ion channel gene expression differed both qualitatively and quantitatively across cell types and could distinguish subtle differences in intrinsic electrophysiology. Single-cell transcript profiling of MVN neurons established six functionally distinct cell types and associated marker genes. This strategy is applicable throughout the nervous system and could facilitate the use of molecular genetic tools to examine the behavioral roles of distinct neuronal populations.
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Takashi
T
Kodama
Shiloh
S
Guerrero
Minyoung
M
Shin
Seti
S
Moghadam
Michael
M
Faulstich
Sascha
S
du Lac
D000465:Algorithms; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena; D005784:Gene Amplification; D005819:Genetic Markers; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007473:Ion Channels / Q000235:genetics; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000145:classification*; D016133:Polymerase Chain Reaction; D059010:Single-Cell Analysis; D014726:Vestibular Nuclei / Q000166:cytology / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D005819:Genetic Markers; D007473:Ion Channels; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases