Divergent cAMP signaling differentially regulates serotonin-induced spinal motor plasticity

NEUROPHARMACOLOGY

卷:113

Article

Fields, D. P.¹  Mitchell, G. S.^2,3 

[1] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA

[2] Univ Florida, Dept Phys, Gainesville, FL 32610 USA

[3] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA

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;   

DOI  :  10.1016/j.neuropharm.2016.09.018

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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