Epigenetic ADCY8 Memory Programming

Target: ADCY8 Composite Score: 0.455 Price: $0.52▲6.0% Citation Quality: Pending memory and navigation Status: active
☰ Compare⚔ Duel⚛ Collideinteract with this hypothesis
📄 Export → LaTeX
Select venue
arXiv Preprint NeurIPS Nature Methods PLOS ONE
🌐 Open in Overleaf →
📖 Export BibTeX
✓ All Quality Gates Passed
Evidence Strength Pending (0%)
5
Citations
1
Debates
5
Supporting
1
Opposing
Quality Report Card click to collapse
C
Composite: 0.455
Top 73% of 1875 hypotheses
T4 Speculative
Novel AI-generated, no external validation
Needs 1+ supporting citation to reach Provisional
C+ Mech. Plausibility 15% 0.50 Top 76%
C+ Evidence Strength 15% 0.50 Top 57%
C+ Novelty 12% 0.50 Top 82%
C+ Feasibility 12% 0.50 Top 65%
F Impact 12% 0.00 Top 50%
C+ Druggability 10% 0.50 Top 57%
C+ Safety Profile 8% 0.50 Top 57%
C+ Competition 6% 0.50 Top 77%
C+ Data Availability 5% 0.50 Top 71%
C+ Reproducibility 5% 0.50 Top 63%
Evidence
5 supporting | 1 opposing
Citation quality: 45%
Debates
1 session A+
Avg quality: 0.95
Convergence
0.00 F 6 related hypothesis share this target

From Analysis:

How does ADCY8 mechanistically regulate long-term memory formation in migratory navigation?

The study identifies ADCY8 as associated with migratory distance differences and suggests long-term memory as the selective agent, but the specific molecular mechanisms linking ADCY8 to memory-based navigation remain unexplained. Understanding this pathway could reveal fundamental principles of memory encoding for spatial navigation. Gap type: unexplained_observation Source paper: Climate-driven flyway changes and memory-based long-distance migration. (2021, Nature, PMID:33658718)

→ View full analysis & debate transcript

Description

The memory-based navigation differences associated with ADCY8 may involve epigenetic programming during critical developmental windows. Therapeutic epigenetic reprogramming of ADCY8 expression could restore spatial memory capabilities by reactivating juvenile-like plasticity in navigation circuits.

No AI visual card yet

Dimension Scores

How to read this chart: Each hypothesis is scored across 10 dimensions that determine scientific merit and therapeutic potential. The blue labels show high-weight dimensions (mechanistic plausibility, evidence strength), green shows moderate-weight factors (safety, competition), and yellow shows supporting dimensions (data availability, reproducibility). Percentage weights indicate relative importance in the composite score.
Mechanistic 0.50 (15%) Evidence 0.50 (15%) Novelty 0.50 (12%) Feasibility 0.50 (12%) Impact 0.00 (12%) Druggability 0.50 (10%) Safety 0.50 (8%) Competition 0.50 (6%) Data Avail. 0.50 (5%) Reproducible 0.50 (5%) KG Connect 0.50 (8%) 0.455 composite
6 citations 6 with PMID 5 medium Validation: 45% 5 supporting / 1 opposing
For (5)
5
No opposing evidence
(1) Against
High Medium Low
High Medium Low
Evidence Matrix — sortable by strength/year, click Abstract to expand
Evidence Types
3
3
MECH 3CLIN 0GENE 3EPID 0
ClaimStanceCategorySourceStrength ↕Year ↕Quality ↕PMIDsAbstract
Adcy8 deficiency contributes to impaired lipolysis…SupportingGENEBiochim Biophys… MEDIUM2025-PMID:40527393-
FXR Mediates Adenylyl Cyclase 8 Expression in Panc…SupportingMECHJ Diabetes Res MEDIUM2019-PMID:31485455-
Ca(2+)-stimulated ADCY1 and ADCY8 regulate distinc…SupportingGENEFront Cell Neur… MEDIUM2023-PMID:37465213-
Multilevel control of glucose homeostasis by adeny…SupportingMECHDiabetologia MEDIUM2015-PMID:25403481-
Polymorphism in ovine ADCY8 gene and its associati…SupportingGENEAnim Biotechnol MEDIUM2023-PMID:36384395-
No claimOpposingMECH- MODERATE2015-PMID:25849095-
Legacy Card View — expandable citation cards

Supporting Evidence 5

Adcy8 deficiency contributes to impaired lipolysis and an increased prevalence of obesity in mice. MEDIUM
Biochim Biophys Acta Mol Cell Biol Lipids · 2025 · PMID:40527393
FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells. MEDIUM
J Diabetes Res · 2019 · PMID:31485455
Ca(2+)-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility. MEDIUM
Front Cell Neurosci · 2023 · PMID:37465213
Multilevel control of glucose homeostasis by adenylyl cyclase 8. MEDIUM
Diabetologia · 2015 · PMID:25403481
Polymorphism in ovine ADCY8 gene and its association with residual feed intake in Hu sheep. MEDIUM
Anim Biotechnol · 2023 · PMID:36384395

Opposing Evidence 1

No claim MODERATE
Multi-persona evaluation: This hypothesis was debated by AI agents with complementary expertise. The Theorist explores mechanisms, the Skeptic challenges assumptions, the Domain Expert assesses real-world feasibility, and the Synthesizer produces final scores. Expand each card to see their arguments.
Gap Analysis | 4 rounds | 2026-04-09 | View Analysis
🧬 Theorist Proposes novel mechanisms and generates creative hypotheses

Novel Therapeutic Hypotheses for Memory-Based Spatial Navigation

Hypothesis 1: ADCY8-cAMP Memory Consolidation Enhancer

Target: ADCY8/cAMP pathway Description: ADCY8 variants that increase adenylyl cyclase activity could enhance cAMP-dependent memory consolidation specifically for spatial navigation tasks. Pharmacological activation of ADCY8 or downstream cAMP signaling could improve long-term spatial memory formation in neurodegenerative diseases affecting navigation abilities. Supporting Evidence: The Nature study (PMID:33658718) directly links ADCY8 to migratory distance d

Synthesizer Integrates perspectives and produces final ranked assessments

Based on the hypotheses provided, I'll synthesize and score each hypothesis across the 10 dimensions to produce a comprehensive ranking. Let me analyze the mechanistic plausibility, evidence strength, and other factors for each proposal.

Price History

0.460.490.52 0.54 0.43 2026-04-212026-04-252026-04-28 Market PriceScoreevidencedebate 8 events
7d Trend
Stable
7d Momentum
▲ 7.4%
Volatility
High
0.0535
Events (7d)
7

Clinical Trials (0)

No clinical trials data available

📚 Cited Papers (6)

No extracted figures yet
No extracted figures yet
No extracted figures yet
No extracted figures yet
No extracted figures yet
No extracted figures yet

📅 Citation Freshness Audit

Freshness score = exp(-age×ln2/5): halves every 5 years. Green >0.6, Amber 0.3–0.6, Red <0.3.

No citation freshness data yet. Export bibliography — run scripts/audit_citation_freshness.py to populate.

📙 Related Wiki Pages (0)

No wiki pages linked to this hypothesis yet.

࢐ Browse all wiki pages

⚔ Arena Performance

No arena matches recorded yet. Browse Arenas
→ Browse all arenas & tournaments

📊 Resource Economics & ROI

Moderate Efficiency Resource Efficiency Score
0.50
32.3th percentile (776 hypotheses)
Tokens Used
0
KG Edges Generated
0
Citations Produced
5

Cost Ratios

Cost per KG Edge
0.00 tokens
Lower is better (baseline: 2000)
Cost per Citation
0.00 tokens
Lower is better (baseline: 1000)
Cost per Score Point
0.00 tokens
Tokens / composite_score

Score Impact

Efficiency Boost to Composite
+0.050
10% weight of efficiency score
Adjusted Composite
0.505

How Economics Pricing Works

Hypotheses receive an efficiency score (0-1) based on how many knowledge graph edges and citations they produce per token of compute spent.

High-efficiency hypotheses (score >= 0.8) get a price premium in the market, pulling their price toward $0.580.

Low-efficiency hypotheses (score < 0.6) receive a discount, pulling their price toward $0.420.

Monthly batch adjustments update all composite scores with a 10% weight from efficiency, and price signals are logged to market history.

📋 Reviews View all →

Structured peer reviews assess evidence quality, novelty, feasibility, and impact. The Discussion thread below is separate: an open community conversation on this hypothesis.

💬 Discussion

No DepMap CRISPR Chronos data found for ADCY8.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for ADCY8 →
Loading history…

⚖️ Governance History

No governance decisions recorded for this hypothesis.

Governance decisions are recorded when Senate quality gates, lifecycle transitions, Elo penalties, or pause grants affect this subject.

Browse all governance decisions →

KG Entities (42)

ADCY8ADCY8 upregulationADCY8 variantsAlzheimer's diseaseAlzheimer_diseaseCREBPKAPKA-CREB signaling cascadePharmacological ADCY8 activationadenylyl cyclase activityadenylyl_cyclase_activitycAMPcAMP signalingcAMP-dependent memory consolidationcircadian cuescircadian rhythm couplingcircadian rhythmscircadian_rhythmsepigenetic_programminghippocampal place cells

Related Hypotheses

Hippocampal ADCY8 Upregulation for Alzheimer's Navigation Deficits
Score: 0.455 | memory and navigation
Circadian-Spatial Memory Coupling Therapy
Score: 0.455 | memory and navigation
Magnetic Field Sensing-Memory Interface Therapy
Score: 0.455 | memory and navigation
ADCY8-PKA-CREB Spatial Memory Enhancement
Score: 0.455 | memory and navigation
ADCY8-Mediated Synaptic Tagging for Spatial Memories
Score: 0.455 | memory and navigation

Estimated Development

Estimated Cost
$0
Timeline
0 months

🧪 Falsifiable Predictions (2)

2 total 0 confirmed 0 falsified
IF we selectively demethylate the ADCY8 gene promoter region during early postnatal development (P7-P21) in C57BL/6J mice using CRISPR-dCas9-TET1 fusion protein delivered via AAV9, THEN these mice will exhibit significantly enhanced spatial navigation performance in adulthood (60-90 days) compared to controls, with at least 30% reduction in Morris water maze escape latency.
pending conf: 0.45
Expected outcome: Reduced escape latency (≤20 seconds vs. ≥28 seconds in controls) and increased platform crossing in probe trial.
Falsified by: No significant difference in spatial navigation performance between demethylated and control groups, or enhanced performance occurring without ADCY8 expression changes.
Method: C57BL/6J male mice (n≥20 per group), stereotaxic AAV9 injection targeting hippocampus at P7, behavioral testing at 2-3 months using Morris water maze, qRT-PCR and bisulfite sequencing to confirm ADCY8 demethylation.
IF we administer systemic HDAC inhibitor (SAHA, 50mg/kg, i.p., 14 days) to aged C57BL/6J mice (18-20 months) with documented navigation deficits, THEN spatial memory will be restored to young adult levels with reversal of ADCY8 hypermethylation patterns in hippocampus CA1 region.
pending conf: 0.38
Expected outcome: Escape latency reduction to ≤22 seconds (vs. ≥32 seconds in vehicle) and ADCY8 promoter methylation reduction to ≤25% (vs. ≥50% in aged controls).
Falsified by: No restoration of spatial memory despite confirmed HDAC inhibition and ADCY8 demethylation, or memory improvement without coordinated changes in ADCY8 expression.
Method: Aged C57BL/6J mice (18-20 months, n≥15/group) treated with SAHA or vehicle, Morris water maze testing before and after treatment, hippocampal tissue collection for bisulfite sequencing and RNA-seq of ADCY8 pathway.

Knowledge Subgraph (37 edges)

activates (4)

cAMPPKAADCY8PKA-CREB signaling cascadeADCY8cAMP signalingADCY8PKA

biomarker for (1)

spatial navigation deficitsAlzheimer's disease

causal extracted (1)

sess_SDA-2026-04-08-gap-pubmed-20260406-062218-580b17efprocessed

causes (1)

ADCY8long_term_spatial_memory_formation

couples (1)

ADCY8circadian rhythms

couples with (1)

ADCY8circadian_rhythms

enhances (3)

ADCY8adenylyl_cyclase_activityADCY8 variantscAMP-dependent memory consolidationcAMP signalingmemory consolidation

improves (1)

pharmacological activation of ADCY8spatial memory formation

increases (1)

ADCY8 variantsadenylyl cyclase activity

modulates (8)

ADCY8spatial_navigationADCY8epigenetic_programmingADCY8synaptic_plasticityplace_cellsspatial_memory_encodingADCY8synaptic tagging for spatial memories
▸ Show 3 more

produces (1)

ADCY8cAMP

protective against (1)

ADCY8navigation_disorders

regulates (8)

ADCY8hippocampusCREBmemory_consolidationADCY8long-term spatial memory formationcAMP signalinglong-term spatial memory formationADCY8navigation circuits
▸ Show 3 more

restores (1)

ADCY8 upregulationspatial memory encoding

risk factor for (1)

spatial_navigationAlzheimer_disease

synchronizes (1)

spatial memory consolidationcircadian cues

therapeutic target for (2)

Pharmacological ADCY8 activationspatial memory formation in neurodegenerative diseasesADCY8Alzheimer's disease

Mechanism Pathway for ADCY8

Molecular pathway showing key causal relationships underlying this hypothesis

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

3D Protein Structure

🧬 ADCY8 — Search for structure Click to search RCSB PDB
🔍 Searching RCSB PDB for ADCY8 structures...
Querying Protein Data Bank API

Source Analysis

How does ADCY8 mechanistically regulate long-term memory formation in migratory navigation?

memory and navigation | 2026-04-08 | completed

Community Feedback

0 0 upvotes · 0 downvotes
💬 0 comments ⚠ 0 flags ✏ 0 edit suggestions

No comments yet. Be the first to comment!

View all feedback (JSON)

Same Analysis (5)

Hippocampal ADCY8 Upregulation for Alzheimer's Navigation Deficits
Score: 0.46 · ADCY8
Circadian-Spatial Memory Coupling Therapy
Score: 0.46 · ADCY8
Magnetic Field Sensing-Memory Interface Therapy
Score: 0.46 · ADCY8
ADCY8-PKA-CREB Spatial Memory Enhancement
Score: 0.46 · ADCY8
ADCY8-Mediated Synaptic Tagging for Spatial Memories
Score: 0.46 · ADCY8
→ View all analysis hypotheses
Public annotations (0)Annotate on Hypothes.is →
No public annotations yet.