A non-synaptic mechanism of complex learning: Modulation of intrinsic neuronal excitability.

Training rats in a particularly difficult olfactory discrimination task initiates a period of accelerated learning of other odors, manifested as a dramatic increase in the rats' capacity to acquire memories for new odors once they have learned the first discrimination task, implying that rule learning has taken place. At the cellular level, pyramidal neurons in the piriform cortex, hippocampus and bsolateral amygdala of olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after rule learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP) which is generated by repetitive spike firing, and is maintained by persistent activation of key second messenger systems. Much like late-LTP, the induction of long-term modulation of intrinsic excitability is protein synthesis dependent. Learning-induced modulation of intrinsic excitability can be bi-directional, pending of the valance of the outcome of the learned task. In this review we describe the physiological and molecular mechanisms underlying the rule learning-induced long-term enhancement in neuronal excitability and discuss the functional significance of such a wide spread modulation of the neurons' ability to sustain repetitive spike generation.