Chapter 20 Long-term potentiation and 4-aminopyridine-induced changes in protein and lipid phosphorylation in the hippocampal slice

Many parts of the nervous system show the phenomenon of synaptic plasticity. One of the most intensively studied models for synaptic plasticity is long-term potentiation (LTP) that can be evoked in many parts of the brain by the application of a brief series of high-frequency electrical stimuli. The tetanization of, for instance, the perforant path fibers in the rat hippocampus results in a marked, long-lasting increase in the response of the monosynaptic perforant path-granule cell subsystem to a test stimulus. LTP, which can be evoked in vivo as well as in vitro, has been implicated as a physiological substrate for memory and learning and is thought to be a monosynaptic phenomenon. In vivo, repetitive tetanization of certain brain areas over a period of several days leads to much more generalized electrophysiological responses and epileptiform activity and eventually to generalize convulsions. In vitro, such generalized epileptiform activity may be induced by convulsants, such as 4-aminopyridine. Several lines of evidence point to a crucial role of calcium in LTP and in epileptogenesis. The increased calcium influx during LTP is thought to result postsynaptically in the activation of Ca 2+ -dependent proteases, thereby unmasking postsynaptic glutamate receptors.