Modulation of excitability as a learning and memory mechanism: A molecular genetic perspective

Gene targeting has contributed substantially to the investigation of the neurobiological basis of mammalian learning and memory (L&M). These experiments start with an hypothesis as to a mechanism underlying L&M, then genes of interest are manipulated, and the impact on neuronal physiology and L&M is studied. Previous gene targeting studies have focussed mainly on the role of synaptic plasticity in L&M. Some of those reports provide evidence that processes other than, or additional to, long-term potentiation (LTP) are required for L&M. Accordingly, it is possible that altered neuronal excitability is an essential mechanism. The properties of ion channels determine neuronal excitability and so genetic alteration of ion channel proper-ties is an appropriate method for testing whether the modulation of excitability affects L&M. K(v)beta1.1-deficient mice were the first mutants used to study the role of altered excitability in mammalian L&M. K(v)beta1.1 is a regulatory subunit with a restricted expression pattern in the brain, and it confers fast inactivation on otherwise noninactivating K+ channel subunits. In hippocampal pyramidal neurones K(v)beta1.1-deficiency results in a reduced slow after-hyperpolarisation (sABP), modulation of which is thought to contribute to L&M. The L&M phenotype of the mutants supports this sAHP hypothesis. It is expected that further gene targeting studies on excitability will lead to valuable insights into the processes of L&M. (C) 2001 Elsevier Science Inc. All rights reserved.