5-HT excites globus pallidus neurons by multiple receptor mechanisms

Neuroscience. 2008 Jan 24;151(2):439-51. doi: 10.1016/j.neuroscience.2007.11.003. Epub 2007 Nov 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cations / metabolism
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Globus Pallidus / cytology*
  • Globus Pallidus / drug effects
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Male
  • Neurons / drug effects*
  • Patch-Clamp Techniques
  • Pindolol / analogs & derivatives
  • Pindolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Presynaptic / drug effects
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology
  • Receptors, Serotonin, 5-HT4 / drug effects
  • Receptors, Serotonin, 5-HT4 / physiology
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects


  • Cations
  • Ion Channels
  • Receptors, Presynaptic
  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 7 receptor
  • Receptors, Serotonin, 5-HT4
  • Serotonin
  • cyanopindolol
  • Pindolol