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The Journal of Neuroscience, February 1, 2002, 22(3):718-727

Antioscillatory Effects of Nociceptin/Orphanin FQ in Synaptic Networks of the Rat Thalamus

Susanne Meis, Thomas Munsch, and Hans-Christian Pape

Institut für Physiologie, Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany

Postsynaptic and presynaptic effects of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor, were investigated in an in vitro slice preparation of the rat thalamic reticular nucleus (NRT) and ventrobasal complex (VB). In NRT as well as VB, all tested neurons developed an outward current on application of 1 µM N/OFQ. Basic properties of the N/OFQ-induced current included inward rectification, dependence on extracellular K⁺, reduction by 100 µM Ba⁺, antagonistic effect of [Nphe¹]nociceptin(1-13)NH₂, and sensitivity to internal GDP--S. Miniature IPSCs (mIPSCs) mediated by GABA_A receptors in VB neurons were not affected by 1 µM N/OFQ. In addition, paired-pulse depression of evoked IPSCs was unchanged, indicating a lack of presynaptic effects. By comparison, N/OFQ application resulted in a reduction in frequency of miniature EPSCs (mEPSCs) in a subpopulation of NRT neurons, whereas paired-pulse facilitation of evoked EPSCs was not altered. In either nucleus, current-clamp experiments revealed a hyperpolarization and associated decrease in input resistance in response to N/OFQ. Although N/OFQ had no measurable effect on calcium-mediated burst activity evoked by depolarizing steps from hyperpolarized values of the membrane potential, rebound bursts on relief of hyperpolarizing current steps were decreased. Slow thalamic oscillations induced in vitro by extracellular stimulation were dampened by N/OFQ in VB and NRT, as seen by delayed onset of rhythmic multiple-unit activity and reduction in amplitude and duration. We conclude that N/OFQ reduces the excitability of NRT and VB neurons predominantly through an increase of a G-protein-coupled inwardly rectifying K⁺ conductance.

Key words: thalamus; electrophysiology; patch-clamp; neuropeptide; potassium inward rectifier; synaptic transmission

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Copyright © 2002 Society for Neuroscience  0270-6474/02/223718-10$05.00/0

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