Multiple conductances are modulated by 5-HT receptor subtypes in rat subthalamic nucleus neurons

Firing patterns of subthalamic nucleus (STN) neurons influence normal and abnormal movements. The STN expresses multiple 5-HT receptor subtypes that may regulate neuronal excitability. We used whole-cell patch-clamp recordings to characterize 5-HT receptor-mediated effects on membrane currents in STN neurons in rat brain slices. In 80 STN neurons under voltage-clamp (-70 mV), 5-HT (30 μM) evoked inward currents in 64%, outward currents in 17%, and biphasic currents in 19%. 5-HT-induced outward current was caused by an increased K⁺ conductance (1.4±0.2 nS) and was blocked by the 5-HT_1A antagonist WAY 100135. The 5-HT-evoked inward current, which was blocked by antagonists at 5-HT_2C and/or 5-HT₄ receptors, had two types of current-voltage (I-V) relations. Currents associated with the type 1 I-V relation showed negative slope conductance at potentials <-110 mV and were occluded by Ba²⁺. In contrast, the type 2 I-V relation appeared linear and had positive slope conductance (0.64±0.11 nS). Type 2 inward currents were Ba²⁺-insensitive, and the reversal potential of -19 mV suggests a mixed cation conductance. In STN neurons in which 5-HT evoked inward currents, 5-HT potentiated burst firing induced by N-methyl-d-aspartate (NMDA). But in neurons in which 5-HT evoked outward current, 5-HT slowed NMDA-dependent burst firing. We conclude that 5-HT receptor subtypes can differentially regulate firing pattern by modulating multiple conductances in STN neurons.