226 Self and the Phenomenon of Life
b2726 Self and the Phenomenon of Life: A Biologist Examines Life from Molecules to Humanity “9x6”Fig. 10.8. Changes in post-synaptic neurons in long-term potentiation (LTP). Two
types of glutamate receptors are depicted in the post-synaptic part of the synapse: the
AMPA type receptor which allows sodium ion to enter, triggering action potential; the
NMDA type receptor which regulates the function of AMPA receptor. (A) The left
panel shows the resting stage when the NMDA receptor is blocked by magnesium
(Mg++). Under this condition, the neurotransmitter glutamate hitting the AMPA recep-
tor causes only a small amount of sodium ion (Na+) to enter the post-synaptic neuron.
(B) The right panel shows that, upon high-frequency (tetanic) stimulation, the pre-
synaptic neuron releases more glutamate. The strong depolarization of the post-
synaptic membrane expels the magnesium and unblocks the NMDA receptor, allowing
the influx of calcium (Ca++). The calcium ion combines with the protein calmodulin
(forming Calcium/calmodulin complex) and activates the enzyme calcium/calmodulin
kinase II (CaMKII), which phosphorylates the AMPA receptor, facilitating the influx of
sodium into the post-synaptic neuron, leading to transient potentiation. If the tetanic
stimulation is repeated many times, calcium/calmodulin sends a message to the cell
nucleus (through cyclic AMP, PKA, and MAPK), leading to gene activation and the
synthesis of more glutamate receptors (both NMDA and AMPA) in the post syn-
aptic neuron, along with the increase in the number of dendritic spines, resulting in
synaptic facilitation. In addition, there is a feedback mechanism through which a
retrograde message is sent from the post-synaptic to the pre-synaptic neuron, causing
release of more glutamate. The abbreviations are: NMDA, N-methyl-D-aspartate; AMPA,
alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid. For clarity and simplicity,
intermediary steps from calcium/calmodulin to the AMPA receptor and cell nucleus are
not depicted.