Molecular basis for catecholaminergic neuron diversity

doi:10.1073/pnas.0405340101

Molecular basis for catecholaminergic neuron diversity

^*Rinat Neuroscience, 3155 Porter Drive, Palo Alto, CA 94304; and ^§ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5402

Communicated by Cornelia I. Bargmann, University of California, San Francisco, July 23, 2004 (received for review May 13, 2004)

Abstract

Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and survival factors. In contrast, the transcriptomes of midbrain DA neurons of the substantia nigra and the ventral tegmental area are closely related with <1% of differentially expressed genes. Transcripts implicated in neural plasticity and survival are enriched in ventral tegmental area neurons, consistent with their role in schizophrenia and addiction and their decreased vulnerability in Parkinson's disease. The molecular profiles presented provide a basis for understanding the common and population-specific properties of catecholaminergic neurons and will facilitate the development of selective drugs.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: grimm{at}rinatneuro.com.
↵ ‡ A.R., F.H., and J.G. have filed a patent application covering the methodology and several genes described in this article.
Abbreviations: CA, catecholamine/catecholaminergic; DA, dopamine/dopaminergic; LC, locus coeruleus; NA, noradrenalin/noradrenergic; PD, Parkinson's disease; SN, substantia nigra; VTA, ventral tegmental area; TH, tyrosine hydroxylase; DBH, DA-β-hydroxylase.