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

Gene targeting has contributed substantially to the investigation of the ne urobiological basis of mammalian learning and memory (L&M). These experimen ts 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 re quired for L&M. Accordingly, it is possible that altered neuronal excitabil ity is an essential mechanism. The properties of ion channels determine neu ronal excitability and so genetic alteration of ion channel proper-ties is an appropriate method for testing whether the modulation of excitability af fects 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 regulat ory subunit with a restricted expression pattern in the brain, and it confe rs fast inactivation on otherwise noninactivating K+ channel subunits. In h ippocampal pyramidal neurones K(v)beta1.1-deficiency results in a reduced s low after-hyperpolarisation (sABP), modulation of which is thought to contr ibute to L&M. The L&M phenotype of the mutants supports this sAHP hypothesi s. It is expected that further gene targeting studies on excitability will lead to valuable insights into the processes of L&M. (C) 2001 Elsevier Scie nce Inc. All rights reserved.