Effects of Alzheimer's pathology on memory function in a biophysical model of hippocampal CA3

Among the pathological hallmarks of Alzheimer's disease (AD) are cholinergic deprivation and extracellular plaques comprised the amyloid /spl beta/-peptide (A/spl beta/). Here their effects on cellular neurophysiology and network autoassociative function are assessed in a simulation of hippocampal area CA3 comprised of biophysical cellular models. Cholinergic denervation is found to slow the intrinsic gamma rhythm of the network, resulting in fewer iterations to converge to stored memory patterns. Acetylcholine (ACh) modulates the firing mode of pyramidal cells from bursting to regular spiking and leads to concomitant changes in dendritic calcium levels. In addition, our simulation of the reported blockade of K/sub A/ channels by A/spl beta/ leads a similar transition in firing mode but increased dendritic calcium accumulation relative to ACh.