Differing influences of dopamine agonists and antagonists on Fos expression in identified populations of globus pallidus neurons.

摘要

Dopamine agonists increase the activity of globus pallidus neurons, as shown electrophysiologically and with Fos expression. More recently it has been shown that decreased D2 receptor activity also causes pallidal Fos expression. Similar responses occur in the striatum, where both dopamine agonists and D2 blockade induce Fos, although in separate neuronal populations (i.e. striatonigral and -pallidal). The present experiments investigate the possible differential dopaminergic regulation of Fos within pallidal neuronal populations, which were classified as parvalbumin-positive or -negative (with parvalbumin immunostaining), or as projecting to various target nuclei (with retrograde transport of FluoroGold iontophoresed into these nuclei). Rats with prior nigrostriatal lesions received saline, D1 agonist, or D2 agonist. Rats with no lesions received saline, combined D1/D2 agonists, or the D2 antagonist eticlopride. Two hours after drug injection, rats were perfused and their brains processed for double-labeling: either Fos staining with parvalbumin staining, or Fos or parvalbumin staining in FluoroGold-labeled sections. Overall, dopamine drug treatments induced more Fos in parvalbumin-negative than -positive cells. However, unlike dopamine agonists, eticlopride induced significant Fos only in the parvalbumin-negative cells. Dopamine agonist-induced Fos was found in pallidal neurons projecting to each of the target nuclei examined, in both normal and nigrostriatal-lesioned rats. Eticlopride-induced Fos occurred only in pallidal neurons projecting to the striatum, providing functional evidence for pallidostriatal cells without axon collaterals to other nuclei. It was also found that pallidostriatal neurons were distinguished from other projection populations by a relative lack of parvalbumin immunoreactivity. Pallidal cells respond heterogeneously to dopaminergic treatments based on their projection target and expression of parvalbumin. The smaller Fos responses in parvalbumin-containing cells may be due largely to the calcium buffering by the parvalbumin itself. Also, the pattern of Fos expression in pallidostriatal neurons suggests that dopamine regulates activity in these cells differently than in other projection populations.