Introduction
In 1935 Krebs discovered that the amino acid glutamate increases metabolism in the isolated retina and that it is concentrated in the cerebral gray matter (Krebs, 1935). Hayashi (1952, 1958) first reported on excitatory properties of glutamate on neuronal tissue. Local administration of glutamate on the motor cortex of dogs and primates resulted in motor seizures. Curtis et al. (1959) subsequently demonstrated that glutamate and aspartate, when applied iontophoretically to the cat spinal cord, depolarized neurons. Since the 1960s there has been appreciation of the role of glutamate in the nervous system, and today it is considered the major excitatory neurotransmitter (Fonnum, 1984). It is essential for learning and memory, synaptic plasticity, neuronal survival and, in early development, for proliferation, migration and differentiation of neuronal progenitors and immature neurons (Guerrini et al., 1995; Ikonomidou et al., 1999; Komuro & Rakic, 1993).
Glutamate fulfils its various functions due to its compartmentalization (Fonnum, 1984). The largest pool of glutamate is the metabolic pool. The neuronal pool is located in nerve endings and represents the neurotransmission pool. A separate pool is located in glia and serves the recycling of transmitter glutamate. The smallest glutamate pool is involved in synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Glutamate is released from presynaptic terminals by a calcium-dependent mechanism, is removed subsequently by uptake into the surrounding glial cells and aminated to glutamine.
When released into the synaptic cleft, glutamate acts at the postsynaptic site on receptors (Hollmann & Heinemann, 1994; Nakanishi, 1992).