title: Classifying neuronal subclasses of the cerebellum through constellation pharmacology.
abstract: A pressing need in neurobiology is the comprehensive identification and characterization of neuronal subclasses within the mammalian nervous system. To this end, we used constellation pharmacology as a method to interrogate the neuronal and glial subclasses of the mouse cerebellum individually and simultaneously. We then evaluated the data obtained from constellation-pharmacology experiments by cluster analysis to classify cells into neuronal and glial subclasses, based on their functional expression of glutamate, acetylcholine, and GABA receptors, among other ion channels. Conantokin peptides were used to identify N-methyl-d-aspartate (NMDA) receptor subtypes, which revealed that neurons of the young mouse cerebellum expressed NR2A and NR2B NMDA receptor subunits. Additional pharmacological tools disclosed differential expression of α-amino-3-hydroxy-5-methyl-4-isoxazloepropionic, nicotinic acetylcholine, and muscarinic acetylcholine receptors in different neuronal and glial subclasses. Certain cell subclasses correlated with known attributes of granule cells, and we combined constellation pharmacology with genetically labeled neurons to identify and characterize Purkinje cells. This study illustrates the utility of applying constellation pharmacology to classify neuronal and glial subclasses in specific anatomical regions of the brain.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Kigen J
authors.initials: KJ
authors.lastname: Curtice
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Leavitt
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chase
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Shrinivasan
authors.initials: S
authors.lastname: Raghuraman
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Horvath
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah.
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah russ.teichert@utah.edu.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Teichert
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000145:classification; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification
chemical_list: D007473:Ion Channels; D017981:Receptors, Neurotransmitter
keywords: calcium imaging; classifying neuronal subclasses; conantokin peptides; constellation pharmacology; genetically labeled neurons