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.
Translation 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.
The authors declare no competing financial interests.
We are grateful to Elizabeth Perry and Robert Smith for expert technical assistance. This work was supported by the National Institutes of Health MH083583 and MH094965 to LEO, NS034007 and NS047384 to EK, NS086933 and DA036673 to CH, Simons Foundation SFARI 27444 to CH, Brain and Behavior Research Foundation 21069 to CH, and Alzheimer's Association MNIRGDP-12-258900 to CH.