ENHANCED LTP IN MICE DEFICIENT IN THE AMPA RECEPTOR GLUR2

AMPA receptors (AMPARs) are not thought to be involved in the inductio n of long-term potentiation (LTP), but may be involved in its expressi on via second messenger pathways. However, one subunit of the AMPARs, GluR2, is also known to control Ca2+ influx. To test whether GluR2 pla ys any role in the induction of LTP, we generated mice that lacked thi s subunit. In GluR2 mutants, LTP in the CA1 region of hippocampal slic es was markedly enhanced (2-fold) and nonsaturating, whereas neuronal excitability and paired-pulse facilitation were normal. The 9-fold inc rease in Ca2+ permeability, in response to kainate application, sugges ts one possible mechanism for enhanced LTP. Mutant mice exhibited incr eased mortality, and those surviving showed reduced exploration and im paired motor coordination. These results suggest an important role for GluR2 in regulating synaptic plasticity and behavior.