title: Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules.
abstract: BACKGROUND
  The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson's disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown.
  
  
  RESULTS
  By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains.
  
  
  CONCLUSIONS
  Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.
authors.forename: Alice
authors.initials: A
authors.lastname: Grison
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchelli
authors.forename: Alice
authors.initials: A
authors.lastname: Urzì
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zamparo
authors.forename: Dejan
authors.initials: D
authors.lastname: Lazarevic
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pascarella
authors.forename: Paola
authors.initials: P
authors.lastname: Roncaglia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Giorgetti
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.forename: Christina
authors.initials: C
authors.lastname: Vlachouli
authors.forename: Roberto
authors.initials: R
authors.lastname: Simone
authors.forename: Francesca
authors.initials: F
authors.lastname: Persichetti
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Claudia
authors.initials: C
authors.lastname: Lodovichi
authors.forename: Charles
authors.initials: C
authors.lastname: Plessy
authors.affiliation: SISSA, Area of Neuroscience, via Bonomea 265, 34136 Trieste, Italy. carninci@riken.jp.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
mesh_terms: D000818:Animals; D002460:Cell Line; D016000:Cluster Analysis; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009812:Odorants; D009928:Organ Specificity / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins; D013378:Substantia Nigra / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018035:Receptors, Odorant; D011994:Recombinant Proteins