Ionic conductance determinants of synaptic memory nets and their implications for Alzheimer's disease.

Electrical and chemical signals representing macroscopic "perturbations" in brain networks engage large numbers of transient "microscopic" ionic channel fluctuations in producing long-lasting changes of conductance (and thus potential). Repeated electrical and chemical signals that occur during associative training of living organisms (from mollusc to mammal) can cause ionic conductance changes lasting from days to many weeks. If a stimulus pattern reoccurs with sufficient frequency, voltage-dependent K(+) conductances-responsible for both synaptic and intrinsic membrane currents-become progressively less probabilistic and more deterministic. In effect, more deterministic ion channel functions record in associative memory more deterministic (i.e., higher probability) events in the environment. This memory has been found to be stored within brain networks as ensembles of local dendritic ionic conductance changes distributed throughout brain regions such as the hippocampus and cerebellar cortex. Numerous other studies taken together support the hypothesis that distributed dendritic loci store associative memory, do not involve long-term potentiation, are also loci for Alzheimer's disease (AD) pathophysiology, and can contribute to, if not be responsible for, early memory loss in clinically manifest AD. J. Neurosci. Res. 58:24-32, 1999. Published 1999 Wiley-Liss, Inc.