CREB-Dependent Transcriptional Control and Quantal Changes in Persistent Long-Term Potentiation in Hippocampal Interneurons
Bibliographic record
Abstract
Mounting evidence indicates an important role of long-term synaptic plasticity in hippocampal inhibitory interneurons in learning and memory. The cellular and molecular mechanisms that underlie such persistent changes in synaptic function in interneurons remain, however, largely undetermined. A transcription- and translation-dependent form of long-term potentiation was uncovered at excitatory synapses onto hippocampal interneurons in oriens-alveus (OA-INs) which is induced by activation of type 1 metabotropic glutamate receptors (cL-LTP(mGluR1)). Here, we use (1) a combination of pharmacological siRNA knock-down and overexpression approaches to reveal the molecular mechanisms of transcriptional control via cAMP response element-binding protein (CREB) during induction, and (2) quantal analysis to identify synaptic changes during maintenance of cL-LTP(mGluR1) in rat hippocampus. Induction stimulated CREB phosphorylation in OA-INs via extracellular signal-regulated protein kinase (ERK) signaling. Also, CREB knockdown impaired cL-LTP(mGluR1), whereas CREB overexpression facilitated the induction, demonstrating a necessary and permissive role of CREB via ERK signaling in transcriptional control in cL-LTP(mGluR1). Quantal analysis of synaptic responses during cL-LTP(mGluR1) maintenance revealed an increased number of quanta released, corresponding to enhanced transmitter release and a larger quantal size, indicating enhanced responsiveness to individual quanta. Fluctuation analysis of synaptic currents uncovered an increase in conductance and number of functional postsynaptic receptors contributing to single quanta. Our findings indicate that CREB-dependent transcription is a necessary permissive switch for eliciting persistent presynaptic and postsynaptic quantal changes at excitatory synapses in inhibitory local circuits, uncovering cell type-specific coupling of induction and expression mechanisms during persistent synaptic plasticity which may contribute to hippocampal long-term memory processes.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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".