Journal
MOLECULAR BRAIN
Volume 14, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13041-021-00737-2
Keywords
Synaptic tag and capture; Synapse specificity; Synaptic efficacy; Synaptic potentiation; Heterosynaptic plasticity; Metaplasticity; Learning; Memory
Categories
Funding
- CIHR
- EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health
- Canada Research Chair
- Canadian Institute for Health Research operating Grants [CIHR66975, 84256]
- National Honor Scientist Program of the National Research Foundation - South Korea Government
- Brain Canada Foundation through the Canada Brain Research Fund
- Health Canada
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The study demonstrates that calcium-permeable AMPA receptors are crucial for heterosynaptic metaplasticity. Results show that significant metaplasticity occurs when a strong TBS precedes a weak TBS, and pausing stimulation can largely eliminate this metaplasticity.
The synaptic tag and capture (STC) hypothesis provides an important theoretical basis for understanding the synaptic basis of associative learning. We recently provided pharmacological evidence that calcium-permeable AMPA receptors (CP-AMPARs) are a crucial component of this form of heterosynaptic metaplasticity. Here we have investigated two predictions that arise on the basis of CP-AMPARs serving as a trigger of STC. Firstly, we compared the effects of the order in which we delivered a strong theta burst stimulation (TBS) protocol (75 pulses) and a weak TBS protocol (15 pulses) to two independent inputs. We only observed significant heterosynaptic metaplasticity when the strong TBS preceded the weak TBS. Second, we found that pausing stimulation following either the sTBS or the wTBS for similar to 20 min largely eliminates the heterosynaptic metaplasticity. These observations are consistent with a process that is triggered by the synaptic insertion of CP-AMPARs and provide a framework for establishing the underlying molecular mechanisms.
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