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Adult and immature nervous system are capable of considerable
"plasticity" and unravelling the underlying mechanisms is one of
the principal and most fascinating goals of Neurobiology. A major
contribution to our understanding of neural plasticity has come
from recent studies in excitato- ry amino acids - which are thought
to mediate a large part of the excitatory synaptic transmission on
the brain. Important steps in this explosive field are: 1) the
synthesis of relatively specific antagonists of the N-methyl-D
aspartate (NMDA) and non-NMDA receptors subtypes, 2) the
characterization of the unique features of the NMDA receptor
channel complex notably its voltage dependent Mg++ blockade, its
permeability to calcium and its allosteric modulation by glycine,
3) the demonstration that by virtue of their Ca++ permeability NMDA
receptors are involved in many -but not all -synapses in the
initiation but not the maintennce of long term potentiation (L TP)
an experimented model of learning and memory processes. More recent
studies also indicate tha excitatory amino acids also play an
important role in developmental plasticity in vivo; in cell
cultures low levels of excitatory amino acids have trophic roles
and can inhibit or promote neurite growth. Excitatory amino acids
also play an important role also in other forms of neural
plasticity such as the use dependent permanent changes in neural
circuit produced by brief seizures (epileptogenesis) as well as the
reactive sprouting and neosynapse formation which take place in
epilepsy models and after deafferentiation or lesions.
Human epilepsy is a major public health problem affecting
approximately 2 persons per 1000. It is particularly frequent in
ohildren where convul sions may lead to brain damage and subsequent
seizure activity in adulthood. Temporal lobe epilepsy (synonyms
include limbic epilepsy. psychomotor epilepsy and complex partial
epilepsy) is the most devastating form of epilepsy in the adult
population since: a) it is often extremely resistant to currently
available anticonvulsant drugs (i.e ** it is more resistant than
tonico-clonic or grand mal seizures) and b) it includes loss of
consciousness. thereby limiting performance of many normal
functions and leaving the individual susceptible to bodily injury.
It is also associated with nerve cell loss. in particular in the
hippocampus and other structures of the temporal lobes. In order to
promote an appropriate therapy it is essential to understand the
etiology of seizures and its relationship to brain damage. Basic
research on epilepsy also provides a very useful vehicle to learn
about the way the brain functions under normal conditions. For
instance. much of our present understanding of the mechanisms of
action of GABA and benzo diazepines. control of neuronal activity.
etc. has been derived from such stUdies.
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