Glutamate receptors may be involved in learning and memory

Glutamate is a neurotransmitter that can bind to a variety of receptors, including both metabotropic and ionotropic receptors. The glutamate receptors are divided into several classes because they can be differentially activated by other chemicals that mimic the action of glutamate. One class of ionotropic glutamate receptors is the NMDA receptors, which can be activated by the chemical N-methyl-D-aspartate. Another class of ionotropic glutamate receptors is activated by a different chemical, abbreviated as AMPA.

Glutamate is an excitatory neurotransmitter, so activation of glutamate receptors always results in Na+ entry into the neuron and depolarization. But the timing of the response to activation by these different types of receptors differs significantly: The AMPA receptors allow a rapid influx of Na+ into the postsynaptic cell, while the NMDA receptors allow a slower and longer-lasting influx of Na+. The NMDA receptors also require that the cell be somewhat depolarized through the action of other receptors before their pores will open and permit Na+ influx. When they do open, these re ceptors also allow Ca2+ to enter the cell. Ca2+ ions act as second messengers in the cell and can trigger a variety of long-term cellular changes.

Figure 44.17 shows how the AMPA and NMDA receptors can work in concert. At resting potential, the NMDA receptor is blocked by a magnesium ion (Mg2+). Strong depolarization of the neuron due to other inputs—such as the activation of AMPA receptors—displaces Mg2+ from the NMDA receptors and allows Na+ and Ca2+ to pass through them when they are activated by glutamate. These special properties of the NMDA receptor are probably involved in learning and memory.

Most of the synaptic events we have studied so far happen very quickly. It is therefore a special challenge to understand how the messages carried by action potentials can result in long-term events such as learning and memory. Our understanding of these processes has been greatly affected by a phenomenon called long-term potentiation, or LTP, that was discovered by neurobiologists working with slices of brain kept alive in dishes of culture medium. Using these brain slice preparations, it is possible to stimulate and record from specific brain regions, or even specific neurons.

In the studies leading to the discovery of LTP, experimenters repeatedly stimulated synaptic inputs to a particular neuron and observed the usual action potential response. When the neuron was stimulated many times in rapid succession, however, they found that the properties of the neuron changed. The magnitude of the postsynaptic response was enhanced, or potentiated, and this change lasted for days or weeks.

How does this modification of a synapse occur? The answer in some areas of the brain now seems quite clear. With

Ionotropic Glutamate Receptors Synapse

44.17 Two Ionotropic Glutamate Receptors

(a) AMPA receptors allow rapid influx of Na+ into the postsynaptic cell. (b) NMDA receptors allow both Na+ and Ca2+ to enter the cell, but respond to synaptic input more slowly.

44.17 Two Ionotropic Glutamate Receptors

(a) AMPA receptors allow rapid influx of Na+ into the postsynaptic cell. (b) NMDA receptors allow both Na+ and Ca2+ to enter the cell, but respond to synaptic input more slowly.

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  • hugo
    How is glutamate involved with learning?
    4 years ago

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