Effect of dopamine on synchronous neuronal oscillations in the globus pallidus-subthalamic nucleus network
Changes in the pattern of activity of neurones within the basal ganglia are relevant in the pathophysiology and symptoms of Parkinson’s disease. The globus pallidus (GP) – subthalamic nucleus (STN) network has been proposed to form a pacemaker driving regenerative synchronous bursting activity. In order to test whether this activity can be sustained in vitro a 20o parasagittal slice of mouse midbrain was developed which preserved functional connectivity between the STN and GP. Using single-unit extracellular recording, dopamine (30 µM) produced an excitation of STN cells. This excitation was independent of synaptic transmission and was mimicked by both the D1-like receptor agonist SKF38393 (10 µM) and the D2-like receptor agonist quinpirole (10 µM) but not by the D2-like agonists sulpiride (10 µM) and eticlopride (10 µM). Using whole-recordings, dopamine was shown to induce membrane depolarisation. This depolarisation was caused either by a D1-like receptor mediated increase in a conductance which reversed at -34 mV, consistent with a non-specific cation conductance, or a D2-like receptor mediated decrease in conductance which reversed around -100 mV, consistent with a potassium conductance. Bath application of dopamine altered the pattern of the burst-firing produced by NMDA an apamin towards a more regular pattern. This effect was associated with a decrease in amplitude and increase in frequency of TTX-resistance plateau potentials which underlie the burst activity.