title: Further characterization of preproenkephalin mRNA-containing cells in the rodent globus pallidus.
abstract: The globus pallidus (external pallidum of primates) is an essential nucleus within basal ganglia circuitry, in part because it receives at least one-half of striatal efferent projections. Neurons of the globus pallidus can be divided into subpopulations based on anatomical, physiological, and chemical features. Globus pallidus neurons project to several structures (the striatum, subthalamic nucleus, entopeduncular nucleus, and substantia nigra pars reticulata), have one of two alternative waveforms (positive/negative versus negative/positive), contain either the calcium binding protein parvalbumin or the neuropeptide precursor preproenkephalin mRNA and show differential immediate early gene responses to dopamine receptor agonists and antagonists. The objective of the present study was to characterize in greater detail the preproenkephalin mRNA-containing pallidal neurons using Sprague-Dawley rats. In situ hybridization for preproenkephalin mRNA was combined with immunocytochemical detection of: (i) the neuron-specific nuclear protein, NeuN, (ii) FluoroGold-labeled pallidostriatal and pallidosubthalamic cells, or (iii) Fos induced by either systemic combined D1-class/D2-class dopamine receptor agonists or a D2-class receptor antagonist. These experiments demonstrated that a substantial population (42%) of globus pallidus neurons contains preproenkephalin mRNA, and that globus pallidus neurons retrogradely labeled after FluoroGold injections into the striatum are more frequently preproenkephalinergic, compared to the population of pallidosubthalamic neurons. Furthermore, systemic administration of a D2 receptor antagonist, eticlopride, induced Fos immunoreactivity predominantly in globus pallidus neurons expressing preproenkephalin mRNA, while combined administration of D1 and D2 receptor agonists induced Fos predominantly in pallidal neurons lacking preproenkephalin mRNA.These results support the conclusion that preproenkephalin mRNA identifies one of the two major subpopulations of pallidal neurons. This preproenkephalin mRNA-expressing pallidal subpopulation preferentially targets the striatum and is more readily activated in its immediate early gene expression by D2 receptor antagonists than by dopamine receptor agonists. This projection provides a pallidal substrate for the dopaminergic regulation of striatal information processing.
authors.affiliation: Department of Neurobiology and Behavior, 2215 Bio Sci II, University of California, Irvine, CA 92697-4550, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Hoover
authors.forename: J F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004525:Efferent Pathways / Q000166:cytology / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D005456:Fluorescent Dyes; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013266:Stilbamidines; D014018:Tissue Distribution
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004745:Enkephalins; D005456:Fluorescent Dyes; D009687:Nuclear Proteins; D010320:Parvalbumins; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013266:Stilbamidines; C033660:preproenkephalin