Joanna Peris, Kevin J. Anderson, Thomas W. Vickroy , Michael. A. King, Bruce E. Hunter and Don W. Walker

3. CET-INDUCED CHANGES IN LONG-TERM POTENTIATION (LTP)

A more profound effect of CET on hippocampal function is that CET appears to alter the capacity for synaptic plasticity such as LTP. LTP is defined as a long-term increase in synaptic efficacy induced by exposure of neurons to high-frequency stimulation of excitatory afferent pathways (38, 39). It is generally considered to be a synaptic model or substrate for learning and memory (40, 41). This enduring change, which can last from hours to days (40, 42, 43), is manifested by an increase in the amplitude and the slope of the extracellular recorded EPSP. LTP also results in an increased amplitude and decreased latency of the population spike. LTP is ordinarily divided into three separate processes: 1) induction, 2) maintenance and 3) expression. At the physiological level, the induction of LTP requires cooperativity of synaptic inputs resulting in a threshold depolarization of the postsynaptic membrane.

CET reduces the percentage of hippocampal slices exhibiting LTP of the population spike in hippocampal area CA1 (44). Similar in vivo studies reveal a diminished population spike amplitude after LTP conditioning trains in the dentate gyrus (17). CET reduces the synaptic component of LTP in addition to its effects on the population spike (45). While CET slices exhibit a progressive increase in LTP with successive conditioning trains, the magnitude of the LTP is substantially reduced relative to control slices. This decrement occurs regardless of whether a 48 hr or 5-7 month withdrawal period is given. When hippocampal tissue from CET and sucrose-treated animals was exposed to the GABA_A antagonist, bicuculline methiodide, the CET-produced disruption of LTP is no longer observed (45). These data indicate that the mechanism for the CET-induced decrement in LTP involves activation of GABA_A receptors.