How does the NMDA receptor detect that two neurons fired together? · Grey Matter

The NMDA receptor needs two conditions at once: glutamate bound, which means the presynaptic cell has just released, and a depolarised membrane, which means the postsynaptic cell is active.

How does the NMDA receptor detect that two neurons fired together?

The NMDA receptor needs two conditions at once: glutamate bound, which means the presynaptic cell has just released, and a depolarised membrane, which means the postsynaptic cell is active. At resting voltage a magnesium ion from outside the cell sits in the pore and blocks it even when glutamate is bound; depolarisation, usually from the AMPA receptors beside it or from a spike back-propagating into the dendrite, pushes the magnesium out. Only then does the channel pass current, including calcium. Glutamate alone opens just the AMPA receptors, depolarisation alone opens nothing, and the two together let in the calcium that signals plasticity.