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Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

¹Department of Neurosurgery, University of Tennessee, Neuroscience Institute, Health Science Center, Memphis; and ²Methodist University Hospital, Memphis, Tennessee

Submitted 1 June 2004; accepted in final form 5 October 2004

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 µM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current (I_H) amplitude and voltage-dependence of I_H activation, suggesting that I_H was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT_2/4 receptor agonist -methyl-5-HT and was partially mimicked by 5-HT₂ receptor agonist DOI or 5-HT₄ receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT₄ receptor antagonist SB 23597-190, 5-HT₂ receptor antagonist ketanserin, and 5-HT_2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT₄ and 5-HT_2C receptors.

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