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J Neurophysiol 93: 980-988, 2005. First published September 29, 2004; doi:10.1152/jn.00669.2004
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5-HT Prolongs Ventral Root Bursting Via Presynaptic Inhibition of Synaptic Activity During Fictive Locomotion in Lamprey

Eric J. Schwartz, Tatyana Gerachshenko and Simon Alford

Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois

Submitted 2 July 2004; accepted in final form 25 September 2004

Locomotor pattern generation is maintained by integration of the intrinsic properties of spinal central pattern generator (CPG) neurons in conjunction with synaptic activity of the neural network. In the lamprey, the spinal locomotor CPG is modulated by 5-HT. On a cellular level, 5-HT presynaptically inhibits synaptic transmission and postsynaptically inhibits a Ca2+-activated K+ current responsible for the slow afterhyperpolarization (sAHP) that follows action potentials in ventral horn neurons. To understand the contribution of these cellular mechanisms to the modulation of the spinal CPG, we have tested the effect of selective 5-HT analogues against fictive locomotion initiated by bath application of N-methyl-D-aspartate (NMDA). We found that the 5-HT1D agonist, L694-247, dramatically prolongs the frequency of ventral root bursting. Furthermore, we show that L694-247 presynaptically inhibits synaptic transmission without altering postsynaptic Ca2+ -activated K+ currents. We also confirm that 5-HT inhibits synaptic transmission at concentrations that modulate locomotion. To examine the mechanism by which selective presynaptic inhibition modulates the frequency of fictive locomotion, we performed voltage- and current-clamp recordings of CPG neurons during locomotion. Our results show that 5-HT decreases glutamatergic synaptic drive within the locomotor CPG during fictive locomotion. Thus we conclude that presynaptic inhibition of neurotransmitter release contributes to 5-HT–mediated modulation of locomotor activity.


Address for reprint requests and other correspondence: S. Alford, Univ. of Illinois at Chicago, Dept. of Biological Sciences, 840 W. Taylor, Rm. 4285, Chicago, IL 60607 (E-mail: sta{at}uic.edu)




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