Intrasubthalamic injection of 6-hydroxydopamine induces changes in the firing rate and pattern of subthalamic nucleus neurons in the rat.

Abstract

The subthalamic nucleus (STN) receives dopaminergic projections from the substantia nigra pars compacta (SNc). To investigate the role of direct and indirect dopaminergic influences on STN neurons, the spontaneous activity was studied in four groups of animals: normal rats, rats with intrasubthalamic or intranigral injection of 6-hydroxydopamine (6-OHDA), and sham STN injection rats by using extracellular recordings 4 weeks postsurgery. After intrasubthalamic injection of 6-OHDA, the mean firing rate significantly decreased (7.29 +/- 0.39 spikes/sec, P < 0.01 vs. 11.13 +/- 0.59 spikes/sec in normal or 11.26 +/- 0.57 spikes/sec in sham group), and the percentage of STN neurons discharging regularly decreased significantly (81%, P < 0.05 vs. 90% in normal group or P < 0.01 vs. 92% in sham group) and that of bursty cells increased (19%, P < 0.05 vs. 10%; in normal group or P < 0.01 vs. 8% in sham group). In the group of rats with SNc lesion, the firing rate of subthalamic neurons did not show a significant difference (11.61 +/- 0.81 spikes/sec) compared with normal group. However, the firing pattern was dramatically changed: 74% of cells exhibited bursty pattern and only 26% of cells discharged regularly or slightly irregularly. Immunohistochemical results showed that intrasubthalamic injection of 6-OHDA induced a marked degeneration of dopaminergic cells in the lateral part of the ipsilateral SNc, whereas 6-OHDA injection into the SNc induced a total in situ lesion of dopamine cells. These results suggest that the SNc exerts an excitatory influence on STN neurons and that the loss of this dopaminergic projection could, at least partially, account for the changes in the firing pattern of STN neurons in the 6-OHDA rat model of parkinsonism.