title: Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation.
abstract: BACKGROUND
  The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice.
  
  
  RESULTS
  In this study, we generated short-form-specific gene targeting (KO) mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice.
  
  
  CONCLUSIONS
  These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation.
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. inouenok@yahoo.co.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoue
authors.forename: Harumi
authors.initials: H
authors.lastname: Nakao
authors.forename: Rika
authors.initials: R
authors.lastname: Migishima
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hino
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsui
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hayashi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003213:Conditioning, Psychological; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005615:Freezing; D018390:Gene Targeting; D017781:Genes, Immediate-Early; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry; D008568:Memory / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms