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Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wang, Guo-Du Zhuo, Min |
| Copyright Year | 2002 |
| 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. |
| Starting Page | 15 |
| Ending Page | 23 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jn.physiology.org/content/jn/87/2/732.full.pdf |
| PubMed reference number | 11826042v1 |
| Volume Number | 87 |
| Issue Number | 2 |
| Journal | Journal of neurophysiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 2-Amino-5-phosphonovalerate AMPA Receptors Action Potentials Adenylate Cyclase Afferent neuron Aspartic Acid Auditory recruitment Calmodulin Colforsin Excitatory Amino Acids Ganglia, Spinal Glutamic Acid Inactive - Biochemical Activity Level Kainate Mammals N-Methyl-D-Aspartate Receptors N-Methylaspartate Neocortex Neurotransmitters Posterior Horn Cells Receptors, Kainic Acid Serotonin Structure of posterior gray horn of spinal cord Synapses Synaptic Transmission Tissue fiber |
| Content Type | Text |
| Resource Type | Article |