This research examines the dopaminergic and glutamatergic control of globus pallidus (GP) immediate early and late-gene expression. While the striaturn is the main recipient of dopamine (DA) input from the substantia nigra pars compacta (SNc), other basal ganglia structures, such as the GP, receive synaptic input from the SNc as well. In addition, the GP has reciprocal projections with the subthalamic nucleus (STN) and with the striatum, and projects directly to the output nuclei of the basal ganglia. The GP is therefore critically positioned to influence both up-stream and down-stream basal ganglia information processing. DA has consistently been demonstrated to be a modulatory transmitter, one which can both facilitate and inhibit other neurotransmitter systems. In the GP, decreased DA tone, as in Parkinson's Disease, appears to paradoxically increase gene expression in a sub-population of pallidal neurons that project to the striatum. DA denervation may therefore activate a population of pallidal neurons that are involved in feedback mechanisms to the striatum.
The specific aims are: (1) to determine the population characteristics, via inummocytochemistry for parvalbumin (PV), of pallidal neurons expressing an increase in GAD67 mRNA following nigrostriatal insult or chronic D2 receptor antagonism and (2) to examine the effects of subthalamic nucleus ablation on 6-OHDA lesion- or D2 antagonist-induced changes in pallidal immediate early- and late-response genes in different pallidal neuron populations. Examination of the interactions of dopamine and glutamate in the GP, will provide information regarding the mechanisms involved in pallidal gene response, and will help clarify the contribution of the globus pallidus to basal ganglia activity, both in intact and in dopamine-denervated states.
| Billings, Lauren M; Marshall, John F (2004) Glutamic acid decarboxylase 67 mRNA regulation in two globus pallidus neuron populations by dopamine and the subthalamic nucleus. J Neurosci 24:3094-103 |
