Abstract

The subthalamic nucleus (STN) plays a pivotal role in normal and abnormal motor function. We used patch pipettes to study effects of 5-HT on synaptic currents evoked in STN neurons by focal electrical stimulation of rat brain slices. 5-HT (10 μM) reduced glutamate-mediated excitatory postsynaptic currents (EPSCs) by 35±4%. However, a much higher concentration of 5-HT (100 μM) was required to inhibit GABA-mediated inhibitory postsynaptic currents (IPSCs) to a comparable extent. Concentration–response curves showed that the 5-HT inhibitory concentration 50% (IC 50) for inhibition of IPSCs (20.2 μM) was more than fivefold greater than the IC 50 for inhibition of EPSCs (3.4 μM). The 5-HT-induced reductions in EPSCs and IPSCs were accompanied by increases in paired-pulse ratios, indicating that 5-HT acts presynaptically to inhibit synaptic transmission. The 5-HT 1B receptor antagonist NAS-181 significantly antagonized 5-HT-induced inhibitions of EPSCs and IPSCs. These studies show that 5-HT inhibits synaptic transmission in the STN by activating presynaptic 5-HT 1B receptors.

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