Abstract
Synapse clustering facilitates circuit integration, learning, and memory. Long-term potentiation (LTP) of mature neurons produces synapse enlargement balanced by fewer spines, raising the question of how clusters form despite this homeostatic regulation of total synaptic weight. Three-dimensional reconstruction from serial section electron microscopy (3DEM) revealed the shapes and distributions of smooth endoplasmic reticulum (SER) and polyribosomes, subcellular resources important for synapse enlargement and spine outgrowth. Compared to control stimulation, synapses were enlarged two hours after LTP on resource-rich spines containing polyribosomes (4% larger than control) or SER (15% larger). SER in spines shifted from a single tubule to complex spine apparatus after LTP. Negligible synapse enlargement (0.6%) occurred on resource-poor spines lacking SER and polyribosomes. Dendrites were divided into discrete synaptic clusters surrounded by asynaptic segments. Spine density was lowest in clusters having only resource-poor spines, especially following LTP. In contrast, resource-rich spines preserved neighboring resource-poor spines and formed larger clusters with elevated total synaptic weight following LTP. These clusters also had more shaft SER branches, which could sequester cargo locally to support synapse growth and spinogenesis. Thus, resources appear to be redistributed to synaptic clusters with LTP-related synapse enlargement while homeostatic regulation suppressed spine outgrowth in resource-poor synaptic clusters.
Highlights
In the past decade, much work has revealed that clusters of dendritic spines form a computational unit of synaptic plasticity, learning, and memory[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
By 2 hours following the induction of Long-term potentiation (LTP), the ratio of spines with a spine apparatus to spines with a simple smooth endoplasmic reticulum (SER) tubule was markedly increased relative to control stimulation (Fig. 2E)
Most of the spine SER shifted from a single tubule in the control condition to an elaborate spine apparatus after inducing LTP with theta-burst stimulation (TBS)
Summary
Much work has revealed that clusters of dendritic spines form a computational unit of synaptic plasticity, learning, and memory[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Time (min) non-potentiated synapses would provide a homeostatic mechanism to balance total synaptic weight, measured structurally as summed synaptic surface area along mature dendrites[16] This homeostatic process is disrupted in many disease states[25,26]. Local protein synthesis is another resource that can control the outgrowth of dendritic spines and synapse enlargement during LTP and other forms of plasticity[24,51]. Polyribosomes (which are readily identified through 3DEM)[52,53] provide a conservative estimate of local translation because monosomes (which are not readily identified) are capable of protein translation[54,55] Polyribosomes undergo both rapid and sustained changes in frequency, demonstrating the dynamic state of local protein synthesis following LTP and learning[52,56]. The role of polyribosomes in local spine and synapse clustering is not known
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
