AMPA-receptor channels, depolarization removes Mg2+ block from NMDA-allowing Na+ infux receptor channel, which that depolarizes (with glutamate bound) the postsynaptic allows Ca2+ to enter the membrane postsynaptic cell for LTP induction. Such animals exhibit specific deficits in their learning abilities but behave almost normally otherwise.
How do NMDA receptors mediate LTP? The answer is that these channels, when open, are highly permeable to Ca2+, which acts as an intracellular signal in the postsynaptic cell, triggering a cascade of changes that are responsible for LTP. Thus, LTP is prevented when Ca2+ levels are held artificially low in the postsynaptic cell by injecting the Ca2+ chelator EGTA into it, and LTP can be induced by artificially raising intracellular Ca2+ levels in the cell. Among the long-term changes that increase the sensitivity of the postsynaptic cell to glutamate is the insertion of new AMPA receptors into the plasma membrane (Figure 11–44). In some forms of LTP, changes occur in the presynaptic cell as well, so that it releases more glutamate than normal when it is activated subsequently.
If synapses were capable only of LTP they would quickly become saturated, and thus be of limited value as an information-storage device. In fact, they also exhibit long-term depression (LTD), with the long-term effect of reducing the number of AMPA receptors in the post-synaptic membrane. This feat is accomplished by degrading AMPA receptors after their selective endocytosis. Surprisingly, LTD also requires NMDA receptor activation and a rise in Ca2+. How does Ca2+ trigger opposite effects at the same synapse? It turns out that this bidirectional control of synaptic strength depends on the magnitude of the rise in Ca2+: high Ca2+ levels activate protein kinases and LTP, whereas modest Ca2+ levels activate protein phosphatases and LTD.
There is evidence that NMDA receptors have an important role in synaptic plasticity and learning in other parts of the brain, as well as in the hippocampus. Moreover, they have a crucial role in adjusting the anatomical pattern of synaptic connections in the light of experience during the development of the nervous system.
Thus, neurotransmitters released at synapses, besides relaying transient electrical signals, can also alter concentrations of intracellular mediators that bring about lasting changes in the efficacy of synaptic transmission. However, it is still uncertain how these changes endure for weeks, months, or a lifetime in the face of the normal turnover of cell constituents.
Ion channels form aqueous pores across the lipid bilayer and allow inorganic ions of appropriate size and charge to cross the membrane down their electrochemical gradients at rates about 1000 times greater than those achieved by any known transporter. The channels are “gated” and usually open transiently in response to a specific perturbation in the membrane, such as a change in membrane potential (voltage-gated channels), or the binding of a neurotransmitter to the channel (transmitter-gated channels).
K+-selective leak channels have an important role in determining the resting membrane potential across the plasma membrane in most animal cells.
increased Ca2+ in the cytosol induces postsynaptic cell to insert new AMPA receptors in the plasma membrane, increasing the cell's sensitivity to glutamate
Figure 11–44 The signaling events in longterm potentiation. Although not shown, transmission-enhancing changes can also occur in the presynaptic nerve terminals in LTP, which may be induced by retrograde signals from the postsynaptic cell.
Voltage-gated cation channels are responsible for the amplification and propaga-WHAT WE DON’T KNOW tion of action potentials in electrically excitable cells, such as neurons and skeletal muscle cells. Transmitter-gated ion channels convert chemical signals to electrical