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 studied? Using the fear conditioning paradigm we demonstrate that EphA receptors play roles in memory. We show that post-training surgical anesthesia leads to robust context specific retrograde amnesia in mice, and post-anesthesia activation of EphA receptors induces a significant amelioration of this amnesia. As acquisition was left unaffected and performance factors were found unaltered, we suggest that the amelioration was due to changes in cognition leading to improved memory. Our data represent the first pieces of evidence for the involvement of EphA receptor tyrosine kinase receptors in mammalian memory, a finding that opens a new avenue into the functional analysis of the largest receptor tyrosine kinase subfamily in the brain.
Gerlai
R
R
Neuroscience Department, Genentech, Inc., South San Francisco, CA 94080-4990, USA. gerlai@gene.com
McNamara
A
A
D000648:Amnesia, Retrograde / Q000139:chemically induced / Q000378:metabolism*; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000009:adverse effects; D000818:Animals; D016860:CD4 Immunoadhesins / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D036386:Ephrin-A5; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000378:metabolism; D007649:Ketamine / Q000009:adverse effects; D007858:Learning / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage / Q000378:metabolism*; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D000778:Anesthetics, Dissociative; D016860:CD4 Immunoadhesins; D036386:Ephrin-A5; D007074:Immunoglobulin G; D008565:Membrane Proteins; D007649:Ketamine; D020794:Receptor Protein-Tyrosine Kinases