PT - JOURNAL ARTICLE AU - Lauren M. Billings AU - John F. Marshall TI - Glutamic Acid Decarboxylase 67 mRNA Regulation in Two Globus Pallidus Neuron Populations by Dopamine and the Subthalamic Nucleus AID - 10.1523/JNEUROSCI.5118-03.2004 DP - 2004 Mar 24 TA - The Journal of Neuroscience PG - 3094--3103 VI - 24 IP - 12 4099 - http://www.jneurosci.org/content/24/12/3094.short 4100 - http://www.jneurosci.org/content/24/12/3094.full SO - J. Neurosci.2004 Mar 24; 24 AB - The globus pallidus (GP) consists of two neuron populations, distinguished according to their immunoreactivity for parvalbumin (PV). The PV-immunoreactive (PV+) neurons project preferentially to “downstream” targets such as the subthalamic and entopeduncular nuclei, whereas neurons lacking PV (PV– neurons) project preferentially to the striatum, suggesting a role for PV– cells in feedback to striatal neurons. Although dopamine D2 antagonist administration induces immediate early gene expression preferentially in PV– GP neurons, little is known about long-term regulation of PV– versus PV+ GP neurons. Nigral 6-hydroxydopamine (6-OHDA) lesions or repeated D2-class antagonist injections have been shown to increase pallidal expression of glutamate decarboxylase (GAD67 isoform) mRNA. This increase in GAD67 is believed to be secondary to activation of excitatory subthalamopallidal projections. The current study examined the effects of subthalamic nucleus (STN) lesion on 6-OHDA- or repeated D2 antagonist-induced changes in GP GAD67 mRNA expression in PV+ and PV– neurons. Five or 21 d after nigral 6-OHDA injections or after 3, 7, or 21 d of D2 antagonist administration, GAD67 mRNA increased in both the PV– and PV+ GP neurons, but the magnitude of the increase was significantly greater in PV– neurons. By contrast, STN lesion resulted in declines in GAD67 mRNA in both cell populations, with the decreases in PV+ neurons exceeding those in PV– neurons. Furthermore, STN lesion completely blocked 6-OHDA- or D2 antagonist-induced GAD67 mRNA increases in PV+ cells but only partly offset the GAD67 mRNA increase in PV– pallidal neurons. Thus, the PV+ and PV– neurons are influenced in qualitatively similar ways by dopamine and the STN, but these cell types exhibit contrasting degrees of regulation by the dopaminergic and STN perturbations. This pattern of results has implications for pallidal control of striatal versus downstream basal ganglia nuclei.