Anesthesia induced retrograde amnesia is ameliorated by ephrinA5-IgG in mice: EphA receptor tyrosine kinases are involved in mammalian memory

EphA receptors and their ephrin-A ligands were previously thought to play a role only in embryonic development of the brain. Recently, however, these proteins were shown to be expressed in the adult mouse brain, primarily in the hippocampus, and were implicated in hippocampal synaptic plasticity and learning. What aspects of learning EphA receptors mediate have not been st udied? Using the fear conditioning paradigm we demonstrate that EphA recept ors play roles in memory. We show that post-training surgical anesthesia le ads to robust context specific retrograde amnesia in mice, and post-anesthe sia activation of EphA receptors induces a significant amelioration of this amnesia. As acquisition was left unaffected and performance factors were f ound unaltered, we suggest that the amelioration was due to changes in cogn ition leading to improved memory. Our data represent the first pieces of ev idence for the involvement of EphA receptor tyrosine kinase receptors in ma mmalian memory, a finding that opens a new avenue into the functional analy sis of the largest receptor tyrosine kinase subfamily in the brain. (C) 200 0 Elsevier Science B.V. All rights reserved.