{
  "phase": "4M",
  "status": "LITERATURE-AUDIT-COMPLETE-BEFORE-IMPLEMENTATION",
  "scope": "Adult Drosophila KC-to-MBON plasticity; evidence is not a quantitative calibration of MaleCNS v1.0 synapses",
  "sources": [
    {
      "source": "Stahl et al., eLife 2022",
      "doi": "10.7554/eLife.76712",
      "pmid": "35285796",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8956283/",
      "experiment_type": "in vivo learning protocols with acetylcholine sensor imaging along KC axonal compartments",
      "species_stage": "adult Drosophila melanogaster",
      "compartment": "multiple MB axonal compartments; longitudinally graded",
      "measured_quantity": "learning-related KC acetylcholine release change",
      "finding": "compartmentalized bidirectional ACh-release plasticity; valence and location matter",
      "model_interpretation": "supports an independently represented presynaptic transmitter-efficacy layer, but supplies no MaleCNS edge-specific efficacy or update coefficient"
    },
    {
      "source": "Davidson, Kaushik and Hige, eNeuro 2023",
      "doi": "10.1523/ENEURO.0275-23.2023",
      "pmid": "37848287",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10616905/",
      "experiment_type": "odor-DAN pairing with in vivo MBON calcium, KC acetylcholine and individual bouton calcium imaging",
      "species_stage": "adult female Drosophila melanogaster, 3-6 days after eclosion",
      "compartment": "gamma5/beta-prime-2a and gamma1-pedc; gamma5/beta-prime-2a is related to but not an exact measured MaleCNS edge mapping for y5B'2a",
      "measured_quantity": "compartment-specific KC ACh release and heterogeneous single-bouton calcium signals",
      "finding": "paired DAN activity depressed odor-evoked ACh release, while bulk KC axonal calcium was unchanged; strongly responsive boutons could depress and weakly responsive boutons could potentiate",
      "model_interpretation": "supports local presynaptic efficacy and cautions against assigning identical biological release responses to all terminals; bouton-level parameters are not inferable from MaleCNS neuron-level CSR"
    },
    {
      "source": "Cohn et al., Cell 2015",
      "doi": "10.1016/j.cell.2015.11.019",
      "pmid": "26687359",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4732734/",
      "experiment_type": "ex vivo KC stimulation and MBON electrophysiology with DAN activation",
      "species_stage": "adult Drosophila melanogaster",
      "compartment": "gamma4 and other tested MB domains",
      "measured_quantity": "KC-to-MBON synaptic current and presynaptic modulation",
      "finding": "dopaminergic protocols can potentiate or depress synaptic transmission; temporal order can reverse direction",
      "model_interpretation": "reinforces compartment/timing dependence; does not justify changing frozen Phase 4J timing polarity or eta"
    },
    {
      "source": "Pribbenow et al., eLife 2022",
      "doi": "10.7554/eLife.80445",
      "pmid": "36250621",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9733945/",
      "experiment_type": "MBON receptor-subunit genetics, in vivo receptor dynamics and appetitive/familiarity behavior",
      "species_stage": "adult Drosophila melanogaster",
      "compartment": "M4/M6 and alpha-prime-3-related circuits, not a validated edge-level mapping to current MaleCNS y5B'2a target",
      "measured_quantity": "postsynaptic nAChR alpha5 requirement and alpha2 receptor dynamics",
      "finding": "postsynaptic cholinergic plasticity can contribute to memory induction/expression, with behavior/compartment specificity",
      "model_interpretation": "supports a separate postsynaptic research branch, but no defensible quantitative update for the current y5B'2a MaleCNS compartment; do not run a mixed branch here"
    },
    {
      "source": "Zhang et al., Journal of Neuroscience 2019",
      "doi": "10.1523/JNEUROSCI.1420-19.2019",
      "pmid": null,
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6855682/",
      "experiment_type": "aversive conditioning with presynaptic and postsynaptic calcium imaging",
      "species_stage": "adult Drosophila melanogaster",
      "compartment": "alpha-prime-3",
      "measured_quantity": "pre- and postsynaptic odor-evoked calcium suppression",
      "finding": "both sides showed suppression across a similar post-training period; causality and quantitative partition are unresolved",
      "model_interpretation": "supports mixed mechanisms in some compartments, not automatic transfer of a postsynaptic coefficient to y5B'2a"
    }
  ],
  "mechanism_conclusion": {
    "presynaptic": "direct support for compartment-specific learning-related KC ACh release modulation; exact release probability per MaleCNS edge remains unknown",
    "postsynaptic": "direct support for nAChR-related MBON changes in specific other circuits; no validated quantitative rule for the current target compartment",
    "mixed": "biologically plausible and compartment-dependent, but not justified as one blended MaleCNS y5B'2a rule",
    "timing_pairings": "LTD and opposite-direction changes depend on KC/DAN timing and training protocol; frozen eligibility-v2 is retained, not recalibrated",
    "saturation_recovery": "the cited studies do not identify a universal edge-level saturation/recovery constant for MaleCNS; physical nonnegative E and the pre-existing Phase 4J 25-percent diagnostic bound are explicit engineering assumptions, not measured values"
  },
  "decisions_before_simulation": {
    "main_branch": "PresynapticEfficacy-v1",
    "postsynaptic_branch": "AUDIT-ONLY-NOT-RUN-COMPARTMENT-SPECIFIC-QUANTITATIVE-RULE-UNKNOWN",
    "efficacy_interpretation": "dimensionless per-edge effective KC terminal drive multiplier, not measured release probability",
    "E_initial": 1.0,
    "E_unit_conversion": "one frozen eta_effective_mv increment is converted to a dimensionless per-anatomical-contact fraction by division by frozen W_syn_mv_per_anatomical_synapse; this is an explicit engineering unit convention, not fitted to Phase 4K sensitivity",
    "unbounded_multiplicative_lower_limit": 0.0,
    "bounded_multiplicative_lower_limit": 0.75,
    "bounded_limit_provenance": "Phase 4J frozen max_fractional_depression=0.25, not newly tuned",
    "five_percent_sensitivity_used_for_tuning": false,
    "numeric_efficacy_claimed_as_measured": false,
    "random_heterogeneity_added": false
  }
}