the strength of that synapse instantly strengthens, and that strength of synaptic transmission increase is persistent. This is known as long-term potentiation, and is the most compelling model that we have for how memory traces may be stored in the central nervous system at least on a fairly short-term basis of a few hours.

Conversely, if you give those same inputs low-frequency activation for a period of several minutes, you can cause a decrease in the strength of synaptic transmission. This essentially erases the memory trace that is being stored in the neurocircuit. Memories are stored by the increase of synaptic transmission in neurocircuits, and perhaps are forgotten by the decrease in transmission in those neurocircuits. Both of these events are induced by activity that arrives at the hippocampus, either sensory activity or the lack of sensory activity.

Synapses have two parts, presynaptic and postsynaptic, that are from two separate neurons. The presynaptic neuron puts a synaptic terminal onto a postsynaptic process of another neuron, and these two neurons communicate with each other via the release of a chemical neurotransmitter—excitatory, glutamate-mediated transmission. There are several subtypes of postsynaptic glutamate receptors. One of the subtypes is an AMPA receptor, and another is a NMDA receptor. Both of these receptors are found in the postsynaptic membrane, and both are ionotropic receptors. They open the IM channel when glutamate binds to the extra cellular binding domain. And then current will flow into the postsynaptic cell causing a synaptic current or a synaptic potential.

These two receptors differ in two important ways. First, the AMPA receptor is not voltage-dependent. That is, it will open any time glutamate binds to it, regardless of the membrane potential of the postsynaptic cell. The NMDA receptor is voltage-dependent. It will open only when the postsynaptic cell is depolarized. In fact, the NMDA receptor opens, but it is blocked by magnesium ions in a voltage-dependent way. Only if you can depolarize the postsynaptic cells efficiently, can you actually get current flow through that NMDA receptor. In summary, AMPA receptors are not voltage-dependent, and NMDA receptors are voltage-dependent.

The second important difference is that the AMPA receptor, when it carries current across the postsynaptic membrane, carries primarily sodium and potassium currents, but no calcium. The NMDA receptor, on the other hand, carries sodium, potassium, and calcium. The triggering factor for both long-term potentiation and long-term depression is the calcium that comes into the NMDA receptor. When a lot of calcium comes through the NMDA receptor the strength of the synapse increases, and, conversely when only a little calcium comes through, the strength of the synapse decreases. Finally, there is a pool of AMPA receptors, which are tethered in some intracellular compartment, which are not on the surface,



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