D2 antagonist-induced c-fos in an identified subpopulation of globus pallidus neurons by a direct intrapallidal action.
Much research now supports the view that the dopaminergic innervation of the globus pallidus external segment (GP) influences basal ganglia information processing via pallidal dopamine (DA) D2, D3, and possibly D1 receptors. Systemic DA agonists, or systemic or intrapallidal dopamine D2-class antagonist administration, can induce immediate early gene expression (IEG) in the rat GP. In view of the distinct chemical phenotypes and axonal projections of the GP neurons, it is important to characterize the population(s) of pallidal neurons responding to local DA manipulations. Parvalbumin (PV) immunostaining was used to identify one of the two principal GP neuron populations. Awake, behaving rats received intrapallidal infusions of the dopamine D2 antagonist sulpiride (50 or 100 ng), the D1-class antagonist SCH-23390 (100 ng), the D2-class agonist quinpirole (500 ng), the GABA(A) antagonist picrotoxin (0.25, 0.5 or 1 microg) or bicuculline (20 ng), the GABA(A) agonist muscimol (15 ng) or vehicle. Intrapallidal GABA manipulations were used to assess the likelihood that the effects of the DAergic drugs on Fos induction occurred secondarily to altering intrapallidal GABA release. Using Fos and PV double immunolabeling procedures, we found that several treatments induced GP Fos, but that intrapallidal sulpiride induced Fos almost exclusively in PV-lacking pallidal neurons. No other intrapallidal drug-induced Fos showed similar population specificity. These results support evidence suggesting that GP DA can play a unique and critical role in modulating pallidal neuron function, and that the cessation of pallidal dopamine transmission can activate gene expression within the pallidal neuron subpopulation that maintains extensive axonal projections to caudate-putamen.
Billings
Lauren M
LM
Department of Neurobiology and Behavior, 2205 McGaugh Hall, University of California at Irvine, Irvine, CA 92697-4550, USA.
Marshall
John F
JF
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D018682:GABA Agents / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010320:Parvalbumins / Q000032:analysis; D010852:Picrotoxin / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D001640:Bicuculline; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D018682:GABA Agents; D009118:Muscimol; D010320:Parvalbumins; D010852:Picrotoxin; D016760:Proto-Oncogene Proteins c-fos; D019257:Quinpirole; D017448:Receptors, Dopamine D2; D013469:Sulpiride