NMDA receptors and long-term potentiation
NMDA receptors let calcium in only when glutamate (a neurotransmitter) is bound and the cell is depolarised, and that calcium can produce long-term potentiation, a lasting strengthening of the synapse.
Remember
An NMDA receptor lets calcium in only when glutamate is bound and the cell is already depolarised (less negative inside). That calcium can strengthen the synapse, and this ability of synapses to change is called plasticity.
Memory aid
NMDA is a coincidence detector, opening only when glutamate is present and the cell is already depolarised.
Think of the receptor as needing both signals together before it opens.
Glutamate is the main excitatory neurotransmitter of the central nervous system, and it generally depolarises neurones, so the inside of the cell becomes less negative. Two ionotropic types of its receptor matter here (ionotropic means the receptor is itself an ion channel): AMPA receptors and NMDA receptors.
AMPA receptors open first and give the fast initial depolarisation. NMDA receptors need two things at once. Glutamate needs to be bound, together with a co-agonist such as glycine, and there needs to be enough depolarisation to push out the magnesium ion that plugs the channel at rest. This is the magnesium block, and it is voltage-dependent: depolarisation relieves it.
Only when glutamate is bound and the cell is depolarised enough can calcium enter. Inside the postsynaptic cell (the cell whose NMDA receptors let the calcium in), the calcium starts signalling that can change synaptic strength. Depending on the pattern of activity, it can produce long-term potentiation, a lasting strengthening of the synapse that underlies learning and memory.
This ability of synapses to change is called plasticity. Calcium entry alone does not guarantee potentiation, since the outcome also depends on the activity pattern and the signalling that follows.
Key facts
- Two things at once
- NMDA receptors need glutamate (with a co-agonist such as glycine) bound and enough depolarisation to relieve the magnesium block.
- Role of AMPA receptors
- they mediate the initial fast depolarisation, which helps relieve the magnesium block.
- Calcium entry
- calcium can enter through the NMDA receptor only after the magnesium block is relieved.
- Long-term potentiation
- a lasting strengthening of the synapse that underlies learning and memory.
- Calcium entry alone
- it does not guarantee potentiation, because the outcome depends on the activity pattern and the signalling that follows.
- Blocking NMDA receptors
- this removes the calcium entry that normally follows depolarisation and can strengthen synaptic transmission.
Exam traps
- Sodium entry through AMPA receptors alone does not produce NMDA-dependent potentiation, because that needs a calcium signal. AMPA receptors give the fast depolarisation that helps relieve the magnesium block.
- Depolarisation does not make the magnesium block on NMDA receptors stronger. It relieves the block, because magnesium blocks the channel at resting membrane potentials, so calcium can enter once glutamate and a co-agonist are bound.
- Glutamate does not reduce synaptic strength by preventing calcium entry. NMDA receptor activation permits calcium entry, which can change synaptic strength.
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