Differential phosphorylation modulation of GluN2B at tyrosine 1336 in two types of chemical-induced LTP in hippocampal slices

Synaptic plasticity, i.e., long‐term potentiation (LTP) and long‐term depression (LTD), has been extensively studied as a cellular mechanism of learning and memory. Chemcal‐induced LTP, which is dependent on activation of NMDA receptor, was widely accepted as neuronal model for exploring synaptic plasticity in brain slice or neuronal cultures. However, the phosphorylation regulation of GluN2B, a critical modulatory subunit of NMDA receptor chemical‐induced LTP remains poorly understood. In the present study, we examined the regulation of GluN2B at tyrosine 1336 in two types of chemical‐induced LTP, either by forskolin & rolipram or by glycine‐treated acute hippocampal slices. Elevated phosphorylation level of tyrosine 1336 at GluN2B in forskolin & rolipram‐induced LTP rather than glycine‐induced LTP was observed. Moreover, a similar increment of Src activity was detected, evidenced by higher phosphorylation level of tyrosine 416 at Src. Taken together, our results reveal a diassociated regulation of tyrosine 1336 at GluN2B and tyrosine 416 at Src in forskolin & rolipram‐induced LTP, uncovering phosphorylation site specific modulation in two types of chemical‐induced LTP, thus broadening our understanding of the role of GluN2B in learning and memory. Support or Funding Information This work was funded by National Natural Science Foundation of China Grant No. 31700882 (to B.Z.) and 31600863 (to W.L.), Zhejiang Provincial Natural Science Foundation of China LY20C090004 ( to B.Z) and LY18H090010 to (H.A.), the start‐up fund of Hainan Medical University (to W.L.).