5-HT excites globus pallidus neurons by multiple receptor mechanisms.
Anatomical and neurochemical studies indicated that the globus pallidus receives serotonergic innervation from raphe nuclei but the membrane effects of 5-HT on globus pallidus neurons are not entirely clear. We address this question by applying whole-cell patch-clamp recordings on globus pallidus neurons in immature rat brain slices. Under current-clamp recording, 5-HT depolarized globus pallidus neurons and increased their firing rate, an action blocked by both 5-HT(4) and 5-HT(7) receptor antagonists and attributable to an increase in cation conductance(s). Further experiments indicated that 5-HT enhanced the hyperpolarization-activated inward conductance which is blocked by 5-HT(7) receptor antagonist. To determine if 5-HT exerts any presynaptic effects on GABAergic and glutamatergic inputs, the actions of 5-HT on synaptic currents were studied. At 10 microM, 5-HT increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but had no effect on both the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). However, 5-HT at a higher concentration (50 microM) decreased the frequency but not the amplitude of the mIPSCs, indicating an inhibition of GABA release from the presynaptic terminals. This effect was sensitive to 5-HT(1B) receptor antagonist. In addition to the presynaptic effects on GABAergic neurotransmission, 5-HT at 50 microM had no consistent effects on glutamatergic neurotransmission, significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in 4 of 11 neurons and decreased the frequency of mEPSCs in 3 of 11 neurons. In conclusion, we found that 5-HT could modulate the excitability of globus pallidus neurons by both pre- and post-synaptic mechanisms. In view of the extensive innervation by globus pallidus neurons on other basal ganglia nuclei, this action of 5-HT originated from the raphe may have a profound effect on the operation of the entire basal ganglia network.
Chen
L
L
Department of Physiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Yung
K K L
KK
Chan
Y S
YS
Yung
W H
WH
D000818:Animals; D002412:Cations / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005917:Globus Pallidus / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D002412:Cations; D007473:Ion Channels; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; C047975:cyanopindolol; D010869:Pindolol