title: Arp2/3 and VASP Are Essential for Fear Memory Formation in Lateral Amygdala.
abstract: The actin cytoskeleton is involved in key neuronal functions such as synaptic transmission and morphogenesis. However, the roles and regulation of actin cytoskeleton in memory formation remain to be clarified. In this study, we unveil the mechanism whereby actin cytoskeleton is regulated to form memory by exploring the roles of the major actin-regulatory proteins Arp2/3, VASP, and formins in long-term memory formation. Inhibition of Arp2/3, involved in actin filament branching and neuronal morphogenesis, in lateral amygdala (LA) with the specific inhibitor CK-666 during fear conditioning impaired long-term, but not short-term, fear memory. The inactive isomer CK-689 had no effect on memory formation. We observed that Arp2/3 is colocalized with the actin-regulatory protein profilin in LA neurons of fear-conditioned rats. VASP binding to profilin is needed for profilin-mediated stabilization of actin cytoskeleton and dendritic spine morphology. Microinjection of poly-proline peptide [G(GP5)3] into LA, to interfere with VASP binding to profilin, impaired long-term but not short-term fear memory formation. Control peptide [G(GA5)3] had no effect. Inhibiting formins, which regulate linear actin elongation, in LA during fear conditioning by microinjecting the formin-specific inhibitor SMIFH2 into LA had no effect on long-term fear memory formation. We conclude that Arp2/3 and VASP, through the profilin binding site, are essential for the formation of long-term fear memory in LA and propose a model whereby these proteins subserve cellular events, leading to memory consolidation.
authors.affiliation: Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa , Haifa 3498838, Israel.
authors.forename: Sreetama
authors.identifier: 0000-0001-9528-1025
authors.initials: S
authors.lastname: Basu
authors.affiliation: Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa , Haifa 3498838, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Kustanovich
authors.affiliation: Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa , Haifa 3498838, Israel.
authors.forename: Raphael
authors.initials: R
authors.lastname: Lamprecht
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013871:Thiones / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D015815:Cell Adhesion Molecules; D002491:Central Nervous System Agents; D007211:Indoles; D008840:Microfilament Proteins; D010455:Peptides; D010750:Phosphoproteins; D051304:Profilins; D018091:Receptors, AMPA; D013871:Thiones; D014498:Uracil; D000098662:Vasodilator-Stimulated Phosphoprotein; C543733:CK-0944666; C547376:SMIFH2 compound; C011083:polyproline
keywords: Arp2/3; VASP; amygdala; fear conditioning; formins; learning and memory