SYNAPTIC PLASTICITY IN THE CA1 AREA OF THE HIPPOCAMPUS OF SCRAPIE-INFECTED MICE

Using conventional in vitro extracellular field potential recordings w e have investigated both short-and long-term synaptic plasticity in th e hippocampal CA1 area of mice infected with ME7 scrapie. In agreement with earlier studies, no changes were seen in the properties of the S chaffer collateral-evoked field excitatory postsynaptic potential duri ng the early stages of the disease (up to 160 days, post inoculation, d.p.i) after which time the recorded potentials were seen to attenuate . Also, up to this time no changes were seen in either paired-pulse fa cilitation or post-tetanic potentiation, which are short-term phenomen a associated with brief elevations in presynaptic calcium levels. Howe ver, there was a significant shift from the ability of slices to maint ain long-term potentiation (LTP) from 100 d.p.i. onwards. In all of th ese experiments short-term potentiation (STP) was preserved, suggestin g that from the time that abnormal PrP becomes detectable, or perhaps even earlier, the mechanisms responsible for stabilizing the maintenan ce phase of LTP are impaired. This result is discussed in terms of the relationship between STP and LTP and how this might be compromised by the conversion of cellular prion protein (PrPC) to the scrapie, prote ase resistant form of PrP (PrPSc). (C) 1998 Academic Press.