Gamma-aminobutyric acid(B) receptor activation suppresses stimulus-evoked burst firing in rat substantia nigra reticulata neurons

Abstract

Previous whole-cell patch-pipette studies showed that focal electrical stimulation of the subthalamic nucleus (STN) evokes a long-lasting complex excitatory postsynaptic currents (EPSC) and synaptically evoked bursts of action potentials in substantia nigra pars reticulata (SNR) neurons. Although synaptically evoked bursting may play a role in normal physiology, excessive burst firing correlates with symptoms of Parkinson's disease. We used patch-pipette recordings in rat brain slices to study the effects of baclofen on complex EPSCs and STN-induced burst firing in SNR neurons. Baclofen (1 µM) caused a reversible, 73% reduction in complex EPSCs, and this effect was blocked by the γ-aminobutyric acid(B) antagonist CGP35348 (100 µM). Using the loose-patch method to record extracellular potentials, a lower concentration of baclofen (100 nM) inhibited STN-evoked bursts, while leaving spontaneous firing of action potentials less affected. We suggest that strategies that selectively inhibit burst firing in the SNR might have therapeutic potential in the treatment of Parkinson's disease.

Figure 1

GABA_B receptor-mediated inhibition of complex EPSCs. (a) Representative current traces show that baclofen produces a concentration-dependent and reversible inhibition of complex EPSCs. (b) Averaged results show time-dependent inhibition of complex EPSCs by baclofen (1 μM). Each point is the mean of 9 cells. (c) Representative current traces show that the GABA_B receptor antagonist CGP35348 (100 μM) greatly reduces the action of baclofen (1 μM). (d) Averaged results show block of baclofen-induced inhibition of complex EPSCs by CGP35348 (100 μM). Each point is the mean of 7 cells.

Figure 2

Loose-patch recordings show that 100 nM baclofen inhibits stimulus-evoked firing to a greater extent than inhibition of spontaneous firing. (a) Voltage trace showing that baclofen (100 nM) eliminates the stimulus-evoked burst of action potentials and slows spontaneous firing. (b) Summarized data showing inhibition of stimulus-evoked spike number (n = 7) and spontaneous firing rate (n = 8) by 100 nM baclofen. Stimulus-evoked spikes were counted during the 1 sec interval following STN stimulation, whereas spontaneous firing rate was measured in the absence of stimulation. (c) Normalized data from “b” showing that 100 nM baclofen caused a greater reduction in evoked spikes compared to inhibition of spontaneous firing rate. Asterisks indicate significant differences from control (*, P < 0.05; **, P < 0.01).