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Myosin II regulates actin rearrangement-related structural synaptic plasticity during conditioned taste aversion memory extinction

Abstract

Similar to memory formation, memory extinction is also a new learning process that requires synaptic plasticity. Actin rearrangement is fundamental for synaptic plasticity, however, whether actin rearrangement in the infralimbic cortex (IL) plays a role in memory extinction, as well as the mechanisms underlying it, remains unclear. Here, using a conditioned taste aversion (CTA) paradigm, we demonstrated increased synaptic density and actin rearrangement in the IL during the extinction of CTA. Targeted infusion of an actin rearrangement inhibitor, cytochalasin D, into the IL impaired memory extinction and de novo synapse formation. Notably, we also found increased myosin II phosphorylation in the IL during the extinction of CTA. Microinfusion of a specific inhibitor of the myosin II ATPase, blebbistatin (Blebb), into the IL impaired memory extinction as well as the related actin rearrangement and changes in synaptic density. Moreover, the extinction deficit and the reduction of synaptic density induced by Blebb could be rescued by the actin polymerization stabilizer jasplakinolide (Jasp), suggesting that myosin II acts via actin filament polymerization to stabilize synaptic plasticity during the extinction of CTA. Taken together, we conclude that myosin II may regulate the plasticity of actin-related synaptic structure during memory extinction. Our studies provide a molecular mechanism for understanding the plasticity of actin rearrangement-associated synaptic structure during memory extinction.

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Acknowledgments

This study was supported by the National 973 Basic Research Program of China (No. 2012CB911000), National Natural Science Foundation of China (No. 31130026, 31070991), the State Program of National Natural Science Foundation of China for Innovative Research Group (No. 81021001), the China Postdoctoral Science Foundation ( No. 2011M501124 ) and the Independent Innovation Foundation of Shandong University (IIFSDU).

Author information

Correspondence to Zhe-Yu Chen.

Additional information

Ai-Ling Bi and Yue Wang contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Fig. 1 Three-step localization method. (a) Anatomical localization. The IL tissue used for EM analysis was divided into three 500 μm-thick slices and was embedded. (b) Histological localization. HE staining was used to locate the 2 μm-thick semi-thin sections. (c) to (f) show the ultrastructural localization. (c) 7-9 pieces of serial ultrathin sections were collected on a single-slot grid. (d) Rectangles represent visual fields at 5000× magnification per ultrathin section. (e) A representative visual field at 5000× magnification. (f) Identification of the “d” used in the synaptic analysis. (PPT 698 kb)

Supplemental Fig. 2 Representative photographs show the percentage of synaptophysin (SYN) positive area in the IL at 2 hr and 8 hr after extinction training on extinction day 4. (a), (b), (c), (d), and (e) represents naive, No Ext (2 hr), Ext (2 hr), No Ext (8 hr), and Ext (8 hr) group, respectively. (f) Quantification of synaptophysin immunoreactivity (SYN-IR) area percentage in the Naive, No Ext (2 hr), Ext (2 hr), No Ext (8 hr) and Ext (8 hr) groups (*P < 0.05, **P < 0.01, compared with the corresponding No Ext group). (PPT 3166 kb)

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Bi, A., Wang, Y., Zhang, S. et al. Myosin II regulates actin rearrangement-related structural synaptic plasticity during conditioned taste aversion memory extinction. Brain Struct Funct 220, 813–825 (2015). https://doi.org/10.1007/s00429-013-0685-5

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Keywords

  • Actin rearrangement
  • Conditioned taste aversion
  • Extinction
  • Myosin II
  • Synapse