Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors
Bibliographic record
Abstract
A major intracellular messenger implicated in synaptic plasticity and cognitive functions both in health and disease is cyclic GMP (cGMP). Utilizing a photoactivatable guanylyl cyclase (BlgC) actuator to increase cGMP in dentate granule neurons of the hippocampus by light, we studied the effects of spatiotemporal cGMP elevations in synaptic and cognitive functions. At medial perforant path to dentate gyrus (MPP-DG) synapses, we found enhanced long-term potentiation (LTP) of synaptic responses when postsynaptic cGMP was elevated during the induction period. Basal synaptic transmission and the paired-pulse ratio were unaffected, suggesting the cGMP effect on LTP was postsynaptic in origin. In behaving mice implanted with a fiber optic and wireless LED device, their performance following DG photoactivation (5-10 min) was studied in a variety of behavioral tasks. There were enhancements in reference memory and social behavior within tens of minutes following DG BlgC photoactivation, and with time (hours), an anxiogenic effect developed. Thus, postsynaptic cGMP elevations, specifically in the DG and specifically during conditions that evoke synaptic plasticity or during experience, are able to rapidly modify synaptic strength and behavioral responses, respectively. The optogenetics technology and new roles for cGMP in the DG may have applications in brain disorders that are impacted by dysregulated cGMP signaling, such as Alzheimer's disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".