ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
ADCY8-PKA-CREB Spatial Memory Enhancement
The complete ADCY8 signaling cascade through PKA to CREB transcriptional activation could be the mechanistic link to long-term spatial memory formation.
memory and navigation
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
The complete ADCY8 signaling cascade through PKA to CREB transcriptional activation could be the mechanistic link to long-term spatial memory formation. Selective activation of this pathway during spatial learning phases could enhance memory consolidation for navigation-dependent behaviors in cognitive impairment.
🧬 Mechanism
🔗 Mechanism from KG for ADCY8
Auto-built from this analysis's top knowledge-graph edges.
graph TD
ADCY8["ADCY8"] -->|produces| cAMP["cAMP"]
ADCY8_1["ADCY8"] -->|modulates| spatial_navigation["spatial_navigation"]
ADCY8_2["ADCY8"] -->|activates| PKA_CREB_signaling_cascad["PKA-CREB signaling cascade"]
ADCY8_3["ADCY8"] -->|regulates| long_term_spatial_memory_["long-term spatial memory formation"]
ADCY8_4["ADCY8"] -->|activates| cAMP_signaling["cAMP signaling"]
ADCY8_5["ADCY8"] -->|activates| PKA["PKA"]
ADCY8_6["ADCY8"] -->|regulates| spatial_memory_formation["spatial memory formation"]
ADCY8_7["ADCY8"] -->|regulates| hippocampus["hippocampus"]
ADCY8_8["ADCY8"] -->|causes| long_term_spatial_memory__9["long_term_spatial_memory_formation"]
ADCY8_10["ADCY8"] -->|modulates| epigenetic_programming["epigenetic_programming"]
ADCY8_11["ADCY8"] -->|protective against| navigation_disorders["navigation_disorders"]
ADCY8_12["ADCY8"] -->|modulates| synaptic_plasticity["synaptic_plasticity"]
ADCY8_13["ADCY8"] -->|enhances| adenylyl_cyclase_activity["adenylyl_cyclase_activity"]
ADCY8_14["ADCY8"] -->|couples with| circadian_rhythms["circadian_rhythms"]
ADCY8_variants["ADCY8 variants"] -->|enhances| cAMP_dependent_memory_con["cAMP-dependent memory consolidation"]
style ADCY8 fill:#ce93d8,stroke:#333,color:#000
style cAMP fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_1 fill:#ce93d8,stroke:#333,color:#000
style spatial_navigation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_2 fill:#ce93d8,stroke:#333,color:#000
style PKA_CREB_signaling_cascad fill:#81c784,stroke:#333,color:#000
style ADCY8_3 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory_ fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_4 fill:#ce93d8,stroke:#333,color:#000
style cAMP_signaling fill:#81c784,stroke:#333,color:#000
style ADCY8_5 fill:#ce93d8,stroke:#333,color:#000
style PKA fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_6 fill:#ce93d8,stroke:#333,color:#000
style spatial_memory_formation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_7 fill:#ce93d8,stroke:#333,color:#000
style hippocampus fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_8 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory__9 fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_10 fill:#ce93d8,stroke:#333,color:#000
style epigenetic_programming fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_11 fill:#ce93d8,stroke:#333,color:#000
style navigation_disorders fill:#ef5350,stroke:#333,color:#000
style ADCY8_12 fill:#ce93d8,stroke:#333,color:#000
style synaptic_plasticity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_13 fill:#ce93d8,stroke:#333,color:#000
style adenylyl_cyclase_activity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_14 fill:#ce93d8,stroke:#333,color:#000
style circadian_rhythms fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_variants fill:#ce93d8,stroke:#333,color:#000
style cAMP_dependent_memory_con fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Physiological and pathological roles of protein kinase A in the heart.
Supports
Locomotion activates PKA through dopamine and adenosine in striatal neurons.
Supports
The regulation of PKA signaling in obesity and in the maintenance of metabolic health.
Supports
Smoothened inhibition of PKA at cilia transduces Hedgehog signals.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — ADCY8
No curated PDB or AlphaFold mapping for ADCY8 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ADCY8.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
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Volatility
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Events (7d)
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Total Cost
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🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF AAV-shRNA targeting Adcy8 (or PKA inhibitor H89 at 10 μM icv) is delivered before spatial training in the Object Location Memory task, THEN Adcy8 knockdown or PKA-inhibited mice will show no prefer | Scramble+vehicle mice: >20% discrimination index; Adcy8-knockdown or H89 mice: ≤5% discrimination index | — no observation — | pending | 0.60 |
| IF AAV-hSyn-hM3Dq-mCherry is expressed in dorsal hippocampal CA1 neurons of C57BL/6J mice and CNO (3 mg/kg, i.p.) is administered 30 minutes before daily Morris water maze training sessions (4 trials/ | hM3Dq+CNO group will spend >40% of probe trial time in target quadrant vs. ~25% for controls (Cohen's d > 0.8) | — no observation — | pending | 0.65 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF AAV-hSyn-hM3Dq-mCherry is expressed in dorsal hippocampal CA1 neurons of C57BL/6J mice and CNO (3 mg/kg, i.p.) is administered 30 minutes before daily Morris water maze training sessions (4 trials/day for 5 consecutive days), THEN the hM3Dq-activated group will exhibit a significantly greater per
Predicted outcome: hM3Dq+CNO group will spend >40% of probe trial time in target quadrant vs. ~25% for controls (Cohen's d > 0.8)
Falsification: No significant difference between hM3Dq-activated and control groups on probe trial target quadrant time (p > 0.05, two-tailed t-test) OR hM3Dq-activated group performs worse than controls
pendingconf 60%
IF AAV-shRNA targeting Adcy8 (or PKA inhibitor H89 at 10 μM icv) is delivered before spatial training in the Object Location Memory task, THEN Adcy8 knockdown or PKA-inhibited mice will show no preference for the novel location (discrimination index ~0) while scramble shRNA or vehicle mice will show
Predicted outcome: Scramble+vehicle mice: >20% discrimination index; Adcy8-knockdown or H89 mice: ≤5% discrimination index
Falsification: Adcy8-knockdown or PKA-inhibited mice retain >15% discrimination index in object location memory, indicating functional redundancy or incorrect pathway attribution
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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