cinanserin and cyanopindolol

Serotonergic modulation of precerebellar nuclei may be crucial for the function of the entire cerebellar system. To study the effects of serotonin (5-HT) on neurons located within the pontine nuclei (PN), the main source of cerebellar mossy fibers, we performed standard intracellular recordings from PN neurons in a slice preparation of the rat pontine brain stem. Application of 5 microM 5-HT significantly altered several intrinsic membrane properties of PN neurons. First, it depolarized the somatic membrane potential by 6.5 +/- 3.5 mV and increased the apparent input resistance from 49.5 +/- 14.6 to 62.7 +/- 21.1 MOmega. Second, 5-HT altered the I-V relationship of PN neurons: it decreased the inward rectification in hyperpolarizing direction, but increased it when depolarizing currents were applied. Third, it decreased the rheobase from 0.32 +/- 0.14 to 0.24 +/- 0.14 nA without affecting the firing threshold. Finally, the amplitude of medium-duration after hyperpolarizations was reduced from -14.9 +/- 2.0 to -12.3 +/- 2.4 mV. Together, these 5-HT effects on the intrinsic membrane properties result in an increase in excitability and instantaneous firing rate. In addition, application of 5 microM 5-HT also modulated postsynaptic potentials (PSPs) evoked by electric stimulations within the cerebral peduncle. The amplitude, maximal slope, and integral of these PSPs were reduced to 46.2 +/- 23.4%, 45.7 +/- 23.7%, and 61.4 +/- 28.4% of the control value, respectively. In contrast, we found no change in the decay and voltage dependence of PSPs. To test modulatory effects on short-term synaptic facilitation, we applied pairs of electrical stimuli at intervals between 10 and 1,000 ms. 5-HT selectively enhanced the paired-pulse facilitation for interstimulus-intervals >20 ms. The alteration of paired-pulse facilitation points to a presynaptic site of action for 5-HT effects on synaptic transmission. Pharmacological experiments suggested that pre- and postsynaptic effects of 5-HT were mediated by two different kinds of 5-HT receptors: changes in intrinsic membrane properties were blocked by the 5-HT(2) receptor antagonist cinanserin while the reduction of PSPs was prevented by the 5-HT(1) receptor antagonist cyanopindolol. In conclusion, 5-HT increases the excitability of PN neurons but decreases the synaptic transmission on them. The selective enhancement of synaptic facilitation may, however, allow high-frequency inputs to effectively drive PN neurons, thus the P

Topics: Animals; Cinanserin; Electrophysiology; Nerve Fibers; Pindolol; Pons; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Synaptic Transmission