Figure 8. Mg²⁺ Block of dNMDARs Functions to Suppress dCREB2-b Expression.

(A) Correlation between amounts of dCREB2-b protein and defects in LTM. Wild-type (+/+) and hs-dCREB2-b flies were heat shocked at 35°C for various durations (min) and separated into two groups. One group was used for immunoblotting to quantify the amounts of dCREB2-b protein (upper panel), and the second group was subjected to spaced-training. (Lower panel) LTM scores (one-day memory after spaced training) are plotted against the amounts of dCREB2-b protein in flies heat shocked for the indicated times. The dCREB2-b/tubulin ratio was normalized to that of wild-type without heat shock. As seen from the regression line obtained from wild-type and hs-dCREB2-b flies, the amount of dCREB2-b in elav/dNR1(N631Q) flies is sufficient to disrupt LTM formation.

(B) A model for Mg²⁺ block function in LTM formation. Ca²⁺ influx during correlated activity activates adenylyl cyclase and kinases, including CaMKs, ERK, and PKA, promoting associative learning and dCREB2-dependent induction of LTM-associated genes. Ca²⁺ influx during uncor-related activity, driven by unpaired stimuli and by “minis,” is usually prevented by Mg²⁺ block. In the absence of Mg²⁺ block, low Ca²⁺ influx from unpaired stimuli and minis increases a repressor isoform dCREB2-b, preventing formation of LTM. See also Figure S7.