Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

Yazmín Ramiro-Cortés,Inbal Israely,Domingos Henrique

doi:10.1371/journal.pone.0071155

Yazmín Ramiro-Cortés, Inbal Israely + Show 1 more

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https://doi.org/10.1371/journal.pone.0071155

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Abstract

Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

Highlights

Changes in synaptic weight have been proposed to serve as the physiological basis for learning and memory [1], and the production of new proteins has been shown to be critical for such long lasting processes [2,3]
In order to determine whether protein synthesis dependent synaptic depression leads to structural changes at dendritic spines, we induced a robust form of metabotropic glutamate receptors (mGluRs) mediated long-term depression (LTD) through the brief bath application of the group I mGluR agonist DHPG in mouse hippocampal slice cultures [22]
Across all of the LTD experiments conducted (n = 161 spines, 17 cells), we found that the majority of spines quantified decreased in volume (138 decreased, 8 grew, 15 showed no change, corresponding to 86%, 5%, and 9% of the total, respectively) (Fig. 1 F, total spine shrinkage is shown in the hatched bar, and the grey shaded area within represents eliminated spines), unlike control conditions in which the majority of spines remained stable (9 decreased, 14 grew, 47 showed no change, corresponding to 13%, 20%, and 67% of the total)

Summary

Introduction

Changes in synaptic weight have been proposed to serve as the physiological basis for learning and memory [1], and the production of new proteins has been shown to be critical for such long lasting processes [2,3]. Activity that leads to new protein synthesis can facilitate the expression of plasticity at other sites for up to 1.5 hours and as far as 70 mm away [9] This cooperation between individual sites demonstrates a prolonged period over which dendritic integration of information can occur when new proteins are available. Such potentiation can lead to competition for the expression of plasticity when simultaneously induced at multiple sites, resulting in bidirectional changes in the volumes of those spines [9]. These observations indicate that mechanisms exist for the regulation of spine growth, and for spine shrinkage

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