Gamma-aminobutyric acidB 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 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 GABAB 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.

Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices

“…In fact, we may have underestimated the selectivity of this action of dopamine because evoked spikes were counted up to 100 ms after each stimulus, which would have included some spontaneous spikes as well as evoked spikes. This selective action of dopamine, which we have also demonstrated previously for the GABA B agonist baclofen (Shen & Johnson, 2012), is likely to be related to a preferential inhibition of polysynaptic transmission by dopamine in the STN. Because excessive burst firing in the subthalamonigral pathway is linked to symptoms of Parkinson's disease (Maltete et al 2007; Benedetti et al 2009), suppression of synaptically induced bursts by dopamine might have therapeutic potential in the treatment of this disease.…”