Inhibition of mGluR1 and IP3Rs impairs long-term memory formation in young chicks

Calcium (Ca2+) is involved in a myriad of cellular functions in the brain including synaptic plasticity. However, the role of intracellular Ca2+ stores in memory processing remains poorly defined. The current study explored a role for glutamate-dependent intracellular Ca2+ release in memory processing via blockade of metabotropic glutamate receptor subtype 1 (mGluR1) and inositol (1,4,5)-trisphosphate receptors (IP3Rs). Using a single-trial discrimination avoidance task developed for the young chick, administration of the specific and potent mGluR1 antagonist JNJ16259685 (500 nM, immediately post-training, ic), or the IP3R antagonist Xestospongin C (5 μM, immediately post-training, ic), impaired retention from 90 min post-training. These findings are consistent with mGluR1 activating IP3Rs to release intracellular Ca2+ required for long-term memory formation and have been interpreted within an LTP2 model. The consequences of different patterns of retention loss following ryanodine receptor (RyR) and IP3R inhibition are discussed.