Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons.
- 1 February 2002
- journal article
- research article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 87 (2), 732-739
- https://doi.org/10.1152/jn.00423.2001
Abstract
Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.Keywords
This publication has 67 references indexed in Scilit:
- Driving AMPA Receptors into Synapses by LTP and CaMKII: Requirement for GluR1 and PDZ Domain InteractionScience, 2000
- Silent Synapses Speak UpNeuron, 1997
- Silent Synapses during Development of Thalamocortical InputsNeuron, 1997
- Pre‐ and Post‐synaptic Actions of 5‐Hydroxytryptamine in the Rat Lumbar Dorsal Horn In Vitro: Implications for Somatosensory TransmissionEuropean Journal of Neuroscience, 1996
- Evidence for silent synapses: Implications for the expression of LTPNeuron, 1995
- Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal sliceNature, 1995
- Cloned Glutamate ReceptorsAnnual Review of Neuroscience, 1994
- The TINS/TiPS Lecture the molecular biology of mammalian glutamate receptor channelsTrends in Neurosciences, 1993
- Neurotransmitters in Nociceptive Modulatory CircuitsAnnual Review of Neuroscience, 1991
- Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the ratPain, 1990