Role of Intracellular Calcium Stores and Calcium-Permeable AMPARs in Functional and Structural Plasticity in Mouse Hippocampal Slices
Bibliographic record
Abstract
Memories are internal representations of life that can last in the order of minutes to years, and are largely experience-dependent. For example, the memory of an inconsequential event typically fades, unless they are closely related to a novel event, succinctly explained by the synaptic tag and capture (STC) hypothesis. The formation of short (STM)- or long - term memories (LTM) involve several biochemical changes that either increase or decrease synaptic efficacy. These changes are commonly referred to as Long-term potentiation (LTP) or depression (LTD). LTP can be differentiated into two forms based on their dependence (LTP2) or independence (LTP1) on protein synthesis (PS) and are hypothesized to be analogous to LTM and STM respectively. In both forms of LTP, calcium (Ca2+) signaling plays a vital role. However, Ca2+ has a number of different sources, the relative importance of which is poorly understood. Here I have investigated the role of calcium-permeable (CP)- AMPARs and Ca2+ release from intracellular stores. Using theta burst stimulation (TBS) of varied strength and patterning, I was able to selectively induce LTP1 (wTBS or cTBS) or a combination of LTP1 and 2 (sTBS). Combining these induction protocols with pharmacological agents, I have confirmed the role of CP-AMPARs and demonstrated that intracellular Ca2+ stores are required specifically for LTP2. To investigate STC, I delivered LTP 2 and LTP1 to independent inputs, which resulted in an enhancement of LTP1 due to STC. I confirmed the role of CP-AMPARs and demonstrated the importance of Ca2+ release from intracellular stores during the induction of LTP2 in STC. Furthermore, to address the question of the association between functional and structural plasticity under physiological conditions, I developed a method to monitor both simultaneously using field potential recordings and two-photon imaging, respectively. I found that functional plasticity induced by sTBS is associated with structural plasticity and that the structural plasticity is entirely dependent on the activation of CP-AMPARs. In conclusion, my findings provide novel insights to the synaptic basis of memory formation and highlight the importance of CP-AMPARs and calcium release from intracellular stores in this process.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".