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The hippocampus has been a focus for research on synaptic plasticity, the ability to potentiate transmission at the synapse by repeated stimulation, providing a neural foundation for learning and memory in terms of ‘long-term potentiation’ (LTP) (Bliss and Lømo, 1973). When we learn something, the efficiency of hippocampal synapses increases, facilitating the passage of nerve impulses along a particular circuit. For example, when exposed to a new word, we have to make new connections among certain neurones to deal with it: some neurones in the visual cortex to recognize the spelling, others in the auditory cortex to hear the pronunciation, and still others in the associative regions of the cortex to relate the word to our existing knowledge. All memories of events, words and images correspond to particular activities of neuronal networks that have strengthened interconnections with one another.

As noted, at least half of the synapses in the CNS are glutamatergic. Glutamate is the major excitatory neurotransmitter in the NS. Glutamatergic pathways are linked to many other neurotransmitter pathways, and receptors are found throughout the brain and spinal cord in neurons and glia. As an amino acid and neurotransmitter, glutamate has multiple normal physiological functions and any dysfunction can have profound effects both in disease and injury. At least 30 proteins at, or near, the glutamate synapse control or modulate neuronal excitability. The N-methyl-D-aspartate receptor (NMDA receptor) is a glutamate receptor found in nerve cells. It is activated when glutamate and glycine (or D-serine) bind to it, and when activated it allows positively charged ions to flow through the cell membrane. These are especially important in synaptic plasticity and the encoding and intermediate storage of memory traces, while AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors mediate fast synaptic transmission necessary for memory retrieval (Tsien et al., 1996).

Collingridge and Singer (1990) discovered that excitatory amino acid receptors mediate synaptic transmission at many synapses that display LTP-type synaptic efficiency. These amino acids are one mechanism of synaptic plasticity in health and disease, and alterations in these processes may lead to brain disorders, such as Alzheimer’s disease.