Serotonin increases the incidence of primary afferent-evoked long-term depression in rat deep dorsal horn neurons.
5-hydroxytryptamine (5-HT) is released in spinal cord by descending systems that modulate somatosensory transmission and can potently depress primary afferent-evoked synaptic responses in dorsal horn neurons. Since primary afferent activity-induced long-term potentiation (LTP) may contribute to central sensitization of nociception, we studied the effects of 5-HT on the expression of sensory-evoked LTP and long-term depression (LTD) in deep dorsal horn (DDH) neurons. Whole cell, predominantly current clamp, recordings were obtained from DDH neurons in transverse slices of neonatal rat lumbar spinal cord. The effect of 5-HT on dorsal-root stimulation-evoked synaptic responses was tested before, during, or after high-frequency conditioning stimulation (CS). In most cells (80%), 5-HT caused a depression of the naïve synaptic response. Even though 5-HT depressed evoked responses, CS in the presence of 5-HT was not only still capable of inducing LTD but also increased its incidence from 54% in controls to 88% (P < 0.001). Activation of ligands selective for 5-HT(1A/1B) and 5-HT(1B), but not 5-HT(2A/2C) or 5-HT(3) receptors, best reproduced these actions. 5-HT also potently depressed postconditioning synaptic responses regardless of whether the induced plasticity was LTP or LTD. Our results demonstrate that in addition to depressing the amplitude of evoked sensory input, 5-HT can also control the direction of its long-term modifiability, favoring the expression of LTD. These findings demonstrate cellular mechanisms that may contribute to the descending serotonergic control of nociception.
Garraway
S M
SM
Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada.
Hochman
S
S
D000344:Afferent Pathways / Q000187:drug effects; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001645:Biguanides / Q000494:pharmacology; D001896:Boron Compounds; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D008689:Methacrylates; D008768:Methylmethacrylates; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000145:classification / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D016037:Single-Blind Method; D009435:Synaptic Transmission / Q000187:drug effects
D000662:Amphetamines; D001645:Biguanides; D001896:Boron Compounds; D008689:Methacrylates; D008768:Methylmethacrylates; D009419:Nerve Tissue Proteins; D011810:Quinoxalines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C052561:CGS 12066B; D012701:Serotonin; C065734:1-(3-chlorophenyl)biguanide; C047087:5-carboxamidotryptamine; C049495:Super-bond; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine