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 IC(50) of 0.6+/-0.2 microM. Evoked excitatory postsynaptic currents were also reduced by baclofen concentration-dependently (IC(50) of 1.6+/-0.2 microM), 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.
Shen
K Z
KZ
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, USA.
Johnson
S W
SW
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018755:GABA Agonists; D018080:Receptors, GABA-B; D018698:Glutamic Acid; D001418:Baclofen