Activation of Nigral and Pallidal Dopamine D1-Like Receptors Modulates Basal Ganglia Outflow in Monkeys

Abstract

Kliem MA, Maidment NT, Ackerson LC, Chen S, Smith Y, Wichmann T. Activation of nigral and pallidal dopamine D1-like receptors modulates basal ganglia outflow in monkeys. J Neurophysiol 98: 1489-1500, 2007. First published July 18, 2007; doi:10.1152/jn.00171.2007. Studies of the effects of dopamine in the basal ganglia have focused on the striatum, whereas the functions of dopamine released in the internal pallidal segment (GPi) or in the substantia nigra pars reticulata (SNr) have received less attention. Anatomic and biochemical investigations have demonstrated the presence of dopamine D1-like receptors (D1LRs) in GPi and SNr, which are primarily located on axons and axon terminals of the GABAergic striatopallidal and striatonigral afferents. Our experiments assessed the effects of D1LR ligands in GPi and SNr on local ␥-aminobutyric acid (GABA) levels and neuronal activity in these nuclei in rhesus monkeys. Microinjections of the D1LR receptor agonist SKF82958 into GPi and SNr significantly reduced discharge rates in GPi and SNr, whereas injections of the D1LR antagonist SCH23390 increased firing in the majority of GPi neurons. D1LR activation also increased bursting and oscillations in neuronal discharge in the 3-to 15-Hz band in both structures, whereas D1LR blockade had the opposite effects in GPi. Microdialysis measurements of GABA concentrations in GPi and SNr showed that the D1LR agonist increased the level of the transmitter. Both findings are compatible with the hypothesis that D1LR activation leads to GABA release from striatopallidal or striatonigral afferents, which may secondarily reduce firing of basal ganglia output neurons. The antagonist experiments suggest that a dopaminergic "tone" exists in GPi. Our results support the finding that D1LR activation may have powerful effects on GPi and SNr neurons and may mediate some of the effects of dopamine replacement therapies in Parkinson's disease.

Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats

“…The expression of DAT may decrease following GDNF, 42 and modulation of DA-D 1 receptor function in SN affects basal ganglia function 43,44 and open-field locomotion. 45 DA-D 1 receptor expression was not significantly different in the SN (Figure 7A), striatum (Figure 7B), or NAc (Figure 7D).…”

The Multiple Correspondence Analysis Method and Brain Functional Connectivity: Its Application to the Study of the Non-linear Relationships of Motor Cortex and Basal Ganglia

“…SN and GPi showed some differences in the CC (Figures 6I,K) and in the Pearson and Spearman correlations (Figure 3) with S1 and M1 (negative relationships for the SN and no significant linking for GPi), suggesting a different functional connectivity of GPi and SN with the somatosensory and motor cortex. Although GPi and SN are frequently considered as a single entity in BG models (Albin et al, 1989; Alexander and Crutcher, 1990; Delong, 1990; Tanibuchi et al, 2009), there are biochemical (Windels et al, 2000; Kliem et al, 2007, 2010), odological (Deniau et al, 1982; Nakanishi et al, 1991; Parent et al, 1999; Mailly et al, 2003), and electrophysiological (Wichmann et al, 1999; Kaneda et al, 2005; Kliem et al, 2010; Lafreniere-Roula et al, 2010) data suggesting functional differences between them (Chastan et al, 2009; Nambu, 2011). …”

Update on models of basal ganglia function and dysfunction

“…An example to illustrate the last point is that many basal ganglia neurons and circuits autonomously produce oscillatory firing patterns due to intrinsic membrane properties. Furthermore, the simple models do not take into account more recent anatomical findings, such as the influence of thalamostriatal projections [30], extrastriatal actions of dopamine (e.g., [31]), or brain stem projections of the basal ganglia [32]. …”