Mechanisms of Synaptic Homeostasis and their Influence on Hebbian Plasticity at CA1 Hippocampal Synapses
Bibliographic record
Abstract
Information is transferred between neurons in the brain via electrochemical transmission at specialized cell-cell junctions called synapses. These structures are far from being static, but rather are influenced by plasticity mechanisms that alter features of synaptic transmission as means to build routes of information flow in the brain. Hebbian forms of synaptic plasticity – long-term potentiation and long-term depression – have been well studied and are considered to be the cellular basis of learning and memory, although their positive feedback nature is prone to instability. Neurons are also endowed with homeostatic mechanisms of synaptic plasticity that act to stabilize neural network functions by globally tuning synaptic drive. Precisely how neurons orchestrate this adaptive homeostatic response and how it influences Hebbian forms of synaptic plasticity, however, remains only partially understood. Using a combination of whole-cell electrophysiology, two-photon imaging and glutamate uncaging in organotypic hippocampal slices, I have expanded upon the known repertoire of homeostatic mechanisms that increase excitatory synaptic drive when CA1 hippocampal neurons experience a prolonged period of diminished activity. I found that the subunit composition of AMPA and NMDA receptors, the two major glutamate receptor subtypes at excitatory synapses, are altered which, in addition to increasing synaptic strength, are predicted to change the signaling and integrative properties of synaptic transmission. Moreover, I found that the amount of glutamate released from presynaptic terminals during evoked-transmission is enhanced and that this mechanism might, in part, underlie the uniform cell-wide homeostatic increase in synaptic strengths. Lastly, I found that homeostatic strengthening of synaptic transmission reduced the potential for CA1 synapses to exhibit long-term potentiation, and that this was caused by altered presynaptic release dynamics that impeded plasticity induction. Together, this work highlights several mechanistic strategies employed by neurons to increase excitatory synaptic drive during periods of activity deprivation which, in addition to balancing cellular excitability, alters the metaplastic state of 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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".