Fig. 6.

GluA1 and PKMζ are involved in the maintenance of IC LTP. (a) Pooled data of NASPM (50 μM) on the maintenance of LTP (n = 5 neurons/3 mice), applied 20 min after the LTP induction. (b) Pooled data of ZIP (5 μM) on the maintenance of LTP in the IC, applied 20 min after the LTP induction (n = 5/5). (c) Summary of effect for the maintenance of LTP. There are significant differences comparing LTP with NASPM and ZIP (one-way ANOVA, F_2,21 = 18.94, p < 0.001). (d) Left: A simplified diagram shows that insular cortex (IC) receives projections from the spinal cord and amygdala. Right: A model for IC LTP. Activation of glutamate NMDARs triggers an increase in postsynaptic Ca²⁺ in dendritic spines. Ca²⁺ is an important intracellular signal for triggering a series of biochemical events that contribute to the induction and expression of LTP. After the activation of NMDARs, Ca²⁺ binds to calmodulin (CaM) and leads to activation of Ca²⁺-stimulated AC1 as well as Ca²⁺/CaM-dependent protein kinases. Subsequently, postsynaptic GluA1-containing AMPA receptors may be transferred into synaptic sites and contribute to enhanced synaptic responses. In addition, activation of AC1 leads to activation of PKA. Activation of cAMP-PKA drives the insertion of GluA1 homomers (CP‐AMPARs). PKMζ may maintain LTP by upregulating GluA1–GluA2 heteromers. Insets in a and b are example eEPSC traces at time points indicated by the numbers in the graph. The arrow denotes the time of pairing protocol. Calibration, 50 pA, 50 ms. Error bars represent SEM; ^***p < 0.001.