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.