Fig. 3.

Glutamate is involved in early synapse formation and synapse stabilization. A: Synapse formation: after contact of filopodium and growth cone, cell adhesion molecules provide a bond between pre- and postsynaptic membranes. Prefabricated release packages accumulate and release glutamate, which stimulates the formation of the postsynaptic density (PSD). Synapse stabilization: pre- and postsynaptic activities need to be synchronized, i.e., the postsynaptic membrane needs to depolarize in response to presynaptic glutamate release. Initially, a coincidence of presynaptic glutamate release and postsynaptic depolarization is needed to promote an incorporation of AMPA/kainate receptors into the postsynaptic membrane, which will stabilize the synapse. A more active glutamate system has a higher likelihood of coincidental glutamate release and postsynaptic depolarization. B, C, D: Details of synapse stabilization. B: In the immature synapse, the postsynaptic site initially has only NMDA receptors. NMDA receptors are blocked by Mg ⁺ , which is removed by the activation of the receptor with glutamate and simultaneous depolarization of the cell membrane. In the mature synapse, activation of AMPA/kainate receptors depolarizes the neuron in response to glutamate release and provides the depolarization needed to remove the Mg ⁺ from NMDA receptors. This allows ion flux through the NMDA receptor. The developing synapse has no AMPA/kainate receptors, and an initial postsynaptic depolarization during presynaptic glutamate release is either coincidental or can be carried over from mature, neighboring synapses. C: A coincidence of presynaptic glutamate release and postsynaptic depolarization removes the Mg^{2 +} block and opens NMDA receptors. D: The initial activation of NMDA receptors prompts the incorporation of AMPA/kainate receptors into the postsynaptic membrane. Subsequent glutamate release will trigger depolarization via AMPA/kainate receptors, which assist the opening of NMDA receptors. Activation of postsynaptic CaM kinase II by the NMDA signal transduction pathway is responsible for the incorporation of AMPA receptors (Wu et al., 1996).