PMID- 28855298 OWN - NLM STAT- MEDLINE DCOM- 20180621 LR - 20200530 IS - 1522-1598 (Electronic) IS - 0022-3077 (Print) IS - 0022-3077 (Linking) VI - 118 IP - 5 DP - 2017 Nov 1 TI - Spinal BDNF-induced phrenic motor facilitation requires PKCtheta activity. PG - 2755-2762 LID - 10.1152/jn.00945.2016 [doi] AB - Spinal brain-derived neurotrophic factor (BDNF) is necessary and sufficient for certain forms of long-lasting phrenic motor facilitation (pMF). BDNF elicits pMF by binding to its high-affinity receptor, tropomyosin receptor kinase B (TrkB), on phrenic motor neurons, potentially activating multiple downstream signaling cascades. Canonical BDNF/TrkB signaling includes the 1) Ras/RAF/MEK/ERK MAP kinase, 2) phosphatidylinositol 3-kinase (PI3K)/Akt, and 3) PLCgamma/PKC pathways. Here we demonstrate that spinal BDNF-induced pMF requires PLCgamma/PKCtheta in normal rats but not MEK/ERK or PI3K/Akt signaling. Cervical intrathecal injections of MEK/ERK (U0126) or PI3K/Akt (PI-828; 100 muM, 12 mul) inhibitor had no effect on BDNF-induced pMF (90 min after BDNF; U0126 + BDNF: 59 +/- 14%, PI-828 + BDNF: 59 +/- 8%, inhibitor vehicle + BDNF: 56 +/- 7%; all P >/= 0.05). In contrast, PKCtheta inhibition with theta inhibitory peptide (TIP; 0.86 mM, 12 mul) prevented BDNF-induced pMF (90 min after BDNF; TIP + BDNF: -2 +/- 2%; P