Intraneuronally injected amyloid beta inhibits long-term potentiation in rat hippocampal slices

Nomura I, Takechi H, Kato N. Intraneuronally injected amyloid beta inhibits long-term potentiation in rat hippocampal slices. J Neurophysiol 107: 2526-2531, 2012. First published February 15, 2012; doi:10.1152/jn.00589.2011.-Extracellular accumulation of amyloid beta (A beta) is a hallmark of Alzheimer's disease (AD). It has been reported that extracellular perfusion of A beta inhibits long-term potentiation (LTP), which is strongly related to memory in animal models. However, it has recently been proposed that intracellular A beta may be the first pathological change to occur in AD. Here, we have investigated the effect on LTP of intracellular injection of A beta (A beta(1-40), A beta(1-42)) into hippocampal pyramidal cells using patch-clamp technique. We found that injection of 1 nM A beta(1-42) completely blocked LTP, and extracellular perfusion of a p38 MAPK inhibitor or a metabotropic glutamate receptor blocker reversed these blocking effects on LTP. Furthermore, we have examined the effects of different concentrations of A beta(1-40) and A beta(1-42) on LTP and showed that A beta(1-40) required a 1,000-fold higher concentration to attenuate LTP than 1 nM A beta(1-42). These results indicate that LTP is impaired by A beta injected into genetically wild-type neurons in the sliced hippocampus, suggesting an acute action of intracellular A beta on the intracellular LTP-inducing machinery.