Differential Scaling of Synaptic Molecules within Functional Zones of an Excitatory Synapse during Homeostatic Plasticity
Bibliographic record
Abstract
Homeostatic scaling is a form of synaptic plasticity where individual synapses scale their strengths to compensate for global suppression or elevation of neuronal activity. This process can be studied by measuring miniature EPSP (mEPSP) amplitudes and frequencies following the regulation of activity in neuronal cultures. Here, we demonstrate a quantitative approach to characterize multiplicative synaptic scaling using immunolabelling of hippocampal neuronal cultures treated with tetrodotoxin (TTX) or bicuculline to extract scaling factors for various synaptic proteins. This approach allowed us to directly examine the scaling of presynaptic and postsynaptic scaffolding molecules along with neurotransmitter receptors in primary cultures from mouse and rat hippocampal neurons. We show robust multiplicative scaling of synaptic scaffolding molecules namely, Shank2, PSD95, Bassoon, and AMPA receptor subunits and quantify their scaling factors. We use super-resolution microscopy to calculate scaling factors of surface expressed GluA2 within functional zones of the synapse and show that there is differential and correlated scaling of GluA2 levels within the spine, the postsynaptic density (PSD), and the perisynaptic regions. Our method opens a novel paradigm to quantify relative molecular changes of synaptic proteins within distinct subsynaptic compartments from a large number of synapses in response to alteration of neuronal activity, providing anatomic insights into the intricacies of variability in strength of individual synapses.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".