The molecular basis for electrogenic computation in the brain: you can't step in the same river twice

Neural computation has classically been considered to be a process that depends, in large part, on the integration of excitatory and inhibitory synaptic signals by postsynaptic neurons; these cells generate sequences of action potentials that convey their messages, in turn, to still other neurons. We now appreciate that synaptic activity is a dynamic process that can be altered by mechanisms that include sprouting, pruning, facilitation, potentiation, and depression. But what about the electrogenic properties of neurons, ie the capability of these cells to generate all-or-non action potentials? Recent work indicates that the electrogenic machinery within neurons is also dynamic as a result of plasticity in the expression of sodium channels within the neuronal membrane. Molecular and functional remodeling of electrogenic membrane has been most extensively studied in developing and diseased neurons, but also occurs in the normal brain. The molecular plasticity of electrogenic membrane has important functional implications, since it can retune the neuron, changing its input-output relations.