期刊
NEUROPHARMACOLOGY
卷 113, 期 -, 页码 82-88出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.09.018
关键词
Motor neuron; Phrenic; Spinal cord; Respiratory plasticity; 5-HT7 receptor; 5-HT2 receptor; Exchange protein activated by cAMP; Protein kinase A; EPAC; PKA
资金
- NIH [RO1 HL80209, RO1 HL69064]
- Advanced Opportunity Fellowship at the University of Wisconsin
- NIH NRSA [F30 HL126351]
- University of Wisconsin Medical Scientist Training Program [NIH T32 GM008692]
Spinal metabotropic serotonin receptors encode transient experiences into long-lasting changes in motor behavior (i.e. motor plasticity). While interactions between serotonin receptor subtypes are known to regulate plasticity, the significance of molecular divergence in downstream G protein coupled receptor signaling is not well understood. Here we tested the hypothesis that distinct cAMP dependent signaling pathways differentially regulate serotonin-induced phrenic motor facilitation (pMF); a well-studied model of spinal motor plasticity. Specifically, we studied the capacity of cAMP-dependent protein kinase A (PKA) and exchange protein activated by cAMP (EPAC) to regulate 5-HT2A receptor-induced pMF within adult male rats. Although spinal PKA, EPAC and 5-HT2A each elicit pMF when activated alone, concurrent PKA and 5-HT2A activation interact via mutual inhibition thereby blocking pMF expression. Conversely, concurrent EPAC and 5-HT2A activation enhance pMF expression reflecting additive contributions from both mechanisms. Thus, we demonstrate that distinct downstream cAMP signaling pathways enable differential regulation of 5-HT2A-induced pMF. Conditional activation of independent signaling mechanisms may explain experience amendable changes in plasticity expression (i.e. meta plasticity), an emerging concept thought to enable flexible motor control within the adult central nervous system. Published by Elsevier Ltd.
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