title: The roles of Eph receptors in contextual fear conditioning memory formation.
abstract: Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner.
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Monica
authors.initials: M
authors.lastname: Dines
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Grinberg
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Maria
authors.initials: M
authors.lastname: Vassiliev
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Ram
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Tamir
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel. Electronic address: rlamp@research.haifa.ac.il.
authors.forename: Raphael
authors.initials: R
authors.lastname: Lamprecht
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016548:Prosencephalon / Q000502:physiology*; D036122:Receptor, EphA4 / Q000235:genetics / Q000502:physiology*; D036183:Receptor, EphB2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C586311:Ephb2 protein, mouse; D036122:Receptor, EphA4; D036183:Receptor, EphB2
keywords: EphA4; EphB2; Fear conditioning; Learning and memory