The Requirement of the C-Terminal Domain of GluA1 in Different Forms of Long-Term Potentiation in the Hippocampus Is Age-Dependent
Open accessAbstract
Long-term potentiation (LTP) at glutamatergic synapses is an extensively studied form of long-lasting synaptic plasticity widely regarded as the cellular basis for learning and memory. At the CA1 synapse, there are multiple forms of LTP with distinct properties. Although AMPA gluta-mate receptors (AMPARs) are a key target of LTP expression, whether they are required in all forms of LTP remains unclear. To address this question, we have used our recently developed mouse line, GluA1C2KI, where the c-terminal domain (CTD) of the endogenous GluA1 is replaced by that of GluA2. Unlike traditional GluA1 global or conditional KO mice, GluA1C2KI mice have no changes in basal AMPAR properties or synaptic transmission allowing a better assessment of GluA1 in synaptic plasticity. We previously showed that these mice are impaired in LTP induced by high frequency stimulation (HFS-LTP), but whether other forms of LTP are also affected in these mice is unknown. In this study, we compared various forms of LTP at CA1 synapses be-tween GluA1C2KI and wild-type littermates by using several induction protocols. We show that HFS-LTP is impaired in both juvenile and adult GluA1C2KI mice. The LTP induced by theta-burst stimulation (TBS-LTP) is also abolished in juvenile GluA1C2KI mice. Interestingly, TBS-LTP can still be induced in adult GluA1C2KI mice, but its mechanisms are altered becoming more sensitive to protein synthesis and the extracellular signal-regulated kinase (ERK) inhibitors compared to wild type control. The GluA1C2KI mice are also differentially altered in several forms of LTP in-duced under whole-cell recording paradigms. These results indicate that the CTD of GluA1 is dif-ferentially involved in different forms of LTP at CA1 synapse highlighting the complexity and adaptative potential of LTP expression mechanisms in the hippocampus.
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Deletion of the CTD of GluA1 yields LTP indistinguishable from neighboring control cells.
“Experiments in which the CTD of GluA1 is deleted (Refs. 273–275, but see Refs. 276, 277) express LTP that is indistinguishable from that in neighboring control cells.”
From Synaptic memory and CaMKII (2023) · cites this paper as [277]
The Results section on adult mice (Figure 7B; page unavailable) reports paired-LTP of similar magnitude in GluA1C2KI and wild-type mice. But this paper replaces the GluA1 CTD rather than deleting it, compares mouse groups rather than neighboring cells, and reports impaired LTP with other protocols and in juvenile mice. Its Discussion says a separate CTD-deletion study found that paired-LTP could be induced, not that it was indistinguishable from neighboring controls. (LLM, conf=0.86)
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Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“276, 277) express LTP that is indistinguishable from that in neighboring control cells.”
Result
- Authors
- Liu, A., Ji, H., Ren, Q., Meng, Y., Zhang, H., Collingride, G., Xie, W., & Jia, Z.
- Affiliations
- Southeast University (CN)
- University of Toronto (CA)
- Corresponding author
- Xie, Wei
- Jia, Zhengping
- Venue
- Frontiers in Synaptic Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-10-30
- Volume
- 12
- Pages
- 588785-588785
- ISSN
- 1663-3563 (ISSN-L)
- PMC
- PMC7661473
- OpenAlex
- W3097654994
- Cited by
- 14
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 4
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Synaptic Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Jiangsu Province
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- GluR1, long-term potentiation, CA1 synapses, hippocampus, theta burst stimulation, high-frequency stimulation, synaptic plasticity, protein synthesis, ERK signaling, glutamatergic synapses
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