Yehezkel Ben-Ari – författare

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.