The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 549-564
Copyright ©2002 by the American Physiological Society
Serotonergic Control of Cerebellar Mossy Fiber Activity by
Modulation of Signal Transfer by Rat Pontine Nuclei Neurons
Martin
Möck,
Cornelius
Schwarz, and
Peter
Thier
Abteilung Kognitive Neurologie, Neurologische
Universitätsklinik Tübingen, Auf der Morgenstelle 15, 72076 Tubingen, Germany
Möck, Martin,
Cornelius Schwarz, and
Peter Thier.
Serotonergic Control of Cerebellar Mossy Fiber Activity by
Modulation of Signal Transfer by Rat Pontine Nuclei Neurons. J. Neurophysiol. 88: 549-564, 2002. 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 µM 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 M
.
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 afterhyperpolarizations 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 µM 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-HT2 receptor
antagonist cinanserin while the reduction of PSPs was prevented by the
5-HT1 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 PN may act as a high-pass filter
during periods of 5-HT release.
