Presynaptic GABA_B receptors inhibit synaptic inputs to rat subthalamic neurons

Effects of baclofen on synaptic transmission were studied in rat subthalamic neurons using whole-cell patch clamp recording from brain slices. Focal electrical stimulation of the brain slice evoked GABAergic inhibitory postsynaptic currents and glutamatergic excitatory postsynaptic currents. Baclofen reduced the amplitude of evoked inhibitory postsynaptic currents in a concentration-dependent manner with an IC₅₀ of 0.6±0.2 μM. Evoked excitatory postsynaptic currents were also reduced by baclofen concentration-dependently (IC₅₀ of 1.6±0.2 μM), but baclofen was more potent at reducing the GABA_A receptor inhibitory postsynaptic currents. The GABA_B receptor antagonist CGP 35348 blocked these inhibitory effects of baclofen on evoked inhibitory and excitatory postsynaptic currents. Baclofen increased the paired-pulse ratios of evoked inhibitory and excitatory postsynaptic currents. Furthermore, baclofen reduced the frequency of spontaneous miniature excitatory postsynaptic currents, but had no effect on their amplitude. These results provide evidence for presence of presynaptic GABA_B receptors that modulate both GABA and glutamate release from afferent terminals in the subthalamus.