Coactivation of metabotropic and NMDA receptors is required for LTP induction.

Induction of long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus is dependent on N-methyl-D-aspartate (NMDA) receptor activation. However, NMDA receptor stimulation alone is not adequate to trigger LTP. Results from the present study indicate that, in addition to NMDA receptors, there is a requirement for co-stimulation of a postsynaptic metabotropic glutamate receptor (mGluR). The mGluR involved in eliciting LTP is not antagonized by L-2-amino-3-phosphonopropionic acid (L-AP3, 500 microM), nor is it coupled to phosphoinositide metabolism. We demonstrate that a novel mGluR, which is stimulated by trans-ACPD and is linked to increase in adenosine 3',5'-monophosphate (cAMP), is physiologically relevant to the induction of LTP.