Synaptic plasticity in the CA1 area of the hippocampus of scrapie-infected mice

Using conventional in vitro extracellular field potential recordings we have investigated both short-and long-term synaptic plasticity in the hippocampal CA1 area of mice infected with ME7 scrapie. In agreement with earlier studies, no changes were seen in the properties of the Schaffer collateral-evoked field excitatory postsynaptic potential during 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 facilitation or post-tetanic potentiation, which are short-term phenomena associated with brief elevations in presynaptic calcium levels. However, there was a significant shift from the ability of slices to maintain long-term potentiation (LTP) from 100 d.p.i. onwards. In all of these experiments short-term potentiation (STP) was preserved, suggesting that from the time that abnormal PrP becomes detectable, or perhaps even earlier, the mechanisms responsible for stabilizing the maintenance 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, protease resistant form of PrP (PrPSc). (C) 1998 Academic Press.