Neurobiology of aging, 2012, 33 (8): 1609-1623

Changes in the physiology of CA1 hippocampal pyramidal neurons in preplaque CRND8 mice

Wykes R, Kalmbach A, Eliava M, Waters J

Amyloid- protein (A) is thought to play a central pathogenic role in Alzheimer’s disease. A can impair synaptic transmission, but little is known about the effects of A on intrinsic cellular properties. Here we compared the cellular properties of CA1 hippocampal pyramidal neurons in acute slices from preplaque transgenic (Tg) CRND8 mice and wild-type (Tg) littermates. CA1 pyramidal neurons from Tg mice had narrower action potentials with faster decays than neurons from Tg littermates. Action potential-evoked intracellular Ca2 transients in the apical dendrite were smaller in Tg than in Tg neurons. Resting calcium concentration was higher in Tg than in Tg neurons. The difference in action potential waveform was eliminated by low concentrations of tetraethylammonium ions and of 4-aminopyridine, implicating a fast delayed-rectifier potassium current. Consistent with this suggestion, there was a small increase in immunoreactivity for Kv3.1b in stratum radiatum in Tg mice. These changes in intrinsic properties may affect information flow through the hippocampus and contribute to the behavioral deficits observed in mouse models and patients with early-stage Alzheimer’s disease.