title: Accumulation of Polyribosomes in Dendritic Spine Heads, But Not Bases and Necks, during Memory Consolidation Depends on Cap-Dependent Translation Initiation.
abstract: Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive pavlovian conditioning and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells. Here we used serial electron microscopy reconstructions to quantify polyribosomes in LA dendrites when consolidation was blocked by the cap-dependent initiation inhibitor 4EGI-1. We found that 4EGI-1 depleted polyribosomes in dendritic shafts and selectively prevented their upregulation in spine heads, but not bases and necks, during consolidation. Cap-independent upregulation was specific to spines with small, astrocyte-associated synapses. Our results reveal that cap-dependent initiation is involved in local translation during learning and that local translational control varies with synapse type.SIGNIFICANCE STATEMENTTranslation initiation is a central regulator of long-term memory formation. Local translation in dendrites supports memory by providing necessary proteins at synaptic sites, but it is unknown whether this requires initiation or bypasses it. We used serial electron microscopy reconstructions to examine polyribosomes in dendrites when memory formation was blocked by an inhibitor of translation initiation. This revealed two major pools of polyribosomes that were upregulated during memory formation: one pool in dendritic spine heads that was initiation dependent and another pool in the bases and necks of small spines that was initiation independent. Thus, translation regulation differs between spine types and locations, and translation that occurs closest to individual synapses during memory formation is initiation dependent.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, lo20@nyu.edu.|Allen Institute for Brain Science, Seattle, Washington 90109.
authors.forename: Linnaea E
authors.initials: LE
authors.lastname: Ostroff
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Botsford
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Sofya
authors.initials: S
authors.lastname: Gindina
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Kiriana K
authors.initials: KK
authors.lastname: Cowansage
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.|Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, and.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: LeDoux
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
authors.affiliation: Institute for Behavioral Genetics and.|Department of Integrative Physiology, University of Colorado, Boulder, Colorado 80303.
authors.forename: Charles
authors.initials: C
authors.lastname: Hoeffer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006835:Hydrazones / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D059906:Neuroimaging; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D011132:Polyribosomes / Q000187:drug effects / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C517852:4EGI-1 compound; D006835:Hydrazones; D012333:RNA, Messenger; D013844:Thiazoles
keywords: cap-dependent translation; local translation; pavlovian conditioning; polyribosomes; serial electron microscopy; structural plasticity