The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 1864-1872
Copyright ©2001 by the American Physiological Society

Serotonin Increases the Incidence of Primary Afferent-Evoked Long-Term Depression in Rat Deep Dorsal Horn Neurons

Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada; and Department of Physiology, Emory University, Atlanta, Georgia 30322

Garraway, Sandra M. and Shawn Hochman. Serotonin Increases the Incidence of Primary Afferent-Evoked Long-Term Depression in Rat Deep Dorsal Horn Neurons. J. Neurophysiol. 85: 1864-1872, 2001. 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-HT₃ 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.