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 properties is an appropriate method for testing whether the modulation of excitability affects L&M. K(v)beta 1.1-deficient mice were the first mutants used to study the role of altered excitability in mammalian L&M. K(v)beta 1.1 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 Kv beta 1.1-deficiency results in a reduced slow after-hyperpolarisation (sAHP), 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.
Giese
K P
KP
Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK. p.giese@ucl.ac.uk
Peters
M
M
Vernon
J
J
D000818:Animals; D018390:Gene Targeting; D005824:Genetics, Behavioral; D006624:Hippocampus / Q000502:physiology; D051662:Kv1.1 Potassium Channel; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated
C496947:Kcna1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel