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  2. Role of microtubules in late-associative plasticity of hippocampal Schaffer collateral-CA1 synapses in mice

Role of microtubules in late-associative plasticity of hippocampal Schaffer collateral-CA1 synapses in mice

  • Neurobiol Learn Mem. 2019 Sep;163:107038. doi: 10.1016/j.nlm.2019.107038.
Dongqing Jing 1 Dongxue Li 1 Cheng Peng 1 Ying Chen 1 Thomas Behnisch 2
Affiliations

Affiliations

  • 1 Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
  • 2 Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. Electronic address: behnish@fudan.edu.cn.
Abstract

The microtubule network represents a key scaffolding structure that forms part of the neuronal Cytoskeleton and contributes to biomolecule exchange within neurons. However, researchers have not determined whether an intact microtubule network is required for late associative plasticity. Therefore, the late associative plasticity of field excitatory postsynaptic potentials from two synaptic inputs was analyzed. Synaptic potentiation was induced through alternating tetanization of hippocampal Schaffer-collateral CA1 synaptic populations in acute slices prepared from young-adult C57BL/6 mice. Vincristine was applied to depolymerize microtubules. Vincristine did not alter the phosphorylation levels of plasticity-related pre- or postsynaptic proteins but reduced the level of a Protein Marker of the ER-Golgi intermediate compartment (ERGIC-53/p58). Vincristine did not alter the magnitude or maintenance of the synaptic potentiation evoked by repeated tetanization (3 × 100 stimuli at 100 Hz) of one synaptic population. However, this synaptic potentiation was sensitive to the coapplication of a protein synthesis inhibitor, such as rapamycin, anisomycin or cycloheximide, indicating that protein synthesis has become essential in depolymerized microtubules during the first hour of the synaptic potentiation. The application of vincristine up to a 70 stimuli, 100 Hz tetanization of a second synaptic input prevented the transformation of short-term potentiation into long-term potentiation (LTP), further indicating that intact microtubules are required for the late associative properties of synaptic plasticity. Therefore, activity-dependent synaptic plasticity does not rely on microtubules within the first two hours after tetanization; however, the associative interaction of independent synaptic inputs relies on their proper function. In addition, either new protein synthesis or microtubule-based processes are sufficient to stabilize LTP within the first 3 h after tetanization, and a deficit in synaptic plasticity is only observable when both processes are blocked.

Keywords

Hippocampus; Long-term potentiation; Microtubule; Synaptic plasticity; Synaptic tagging; fEPSP.

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