Version history

{
  "kind": "infographic",
  "prompt": "Gliotransmission: Evidence and Controversy figure 1",
  "provider": "other",
  "raw_fields": {
    "topic": "Effect of manipulating astrocyte signaling on hippocampal NMDAR co-agonist-site occupancy and LTP magnitude",
    "metric": "Change in NMDAR EPSC or LTP amplitude (percent change, baseline-normalized)",
    "papers": [
      {
        "n": 16,
        "doi": "10.1038/nature08673",
        "label": "Henneberger 2010 — single-astrocyte Ca2+ clamp (FAC) suppresses NMDAR fEPSP; exogenous D-serine rescues NMDAR EPSCs",
        "n_FAC": 16,
        "value": "FAC reduces NMDAR fEPSPs by 23 ± 4% (n=16); 10 µM D-serine increases NMDAR EPSCs by 29 ± 10% (n=5)",
        "direction": "decrease (Ca2+ clamp) reversed by exogenous D-serine",
        "n_Dserine": 5,
        "n_analyzed": 16,
        "n_definition": "n = number of slice or cell recordings",
        "scope_region": "Mouse hippocampal CA1 acute slice",
        "taxonomic_level": "slice and single-cell electrophysiology",
        "scope_population": "NMDAR fEPSPs (slice) and NMDAR EPSCs (CA1 pyramidal cell)",
        "value_source_sentence": "Consistent both with these observations and with the Ca 2+ clamp effects, FAC also reduced NMDAR fEPSPs by 23 ± 4% (n = 16, p = 0.00017; Supplementary Fig. In resting conditions, 10 μM D-serine increased NMDAR-mediated excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells (by 29 ± 10%; n = 5, p = 0.039; Fig.",
        "value_source_sentence_FAC": "Consistent both with these observations and with the Ca 2+ clamp effects, FAC also reduced NMDAR fEPSPs by 23 ± 4% (n = 16, p = 0.00017; Supplementary Fig.",
        "value_source_sentence_Dserine": "In resting conditions, 10 μM D-serine increased NMDAR-mediated excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells (by 29 ± 10%; n = 5, p = 0.039; Fig.",
        "numeric_value_reduction_pct_FAC": 23,
        "numeric_value_increase_pct_Dserine_rescue": 29
      },
      {
        "n": 0,
        "doi": "10.1126/science.1184821",
        "label": "Global astrocytic IP3R2 knockout or MrgA1 DREADD activation",
        "value": "No significant effect on evoked EPSCs or synaptic plasticity (qualitative null)",
        "direction": "no_effect",
        "n_analyzed": null,
        "n_definition": "n not reported in abstract — qualitative summary",
        "scope_region": "Mouse hippocampal CA1 acute slice",
        "taxonomic_level": "population-level synaptic measurements",
        "scope_population": "mEPSCs, evoked EPSCs, LTP (multiple measures)",
        "value_source_sentence": "Neither increasing nor obliterating astrocytic Ca2+ fluxes affects spontaneous and evoked excitatory synaptic transmission or synaptic plasticity.",
        "numeric_value_reduction_pct": 0
      },
      {
        "n": 0,
        "doi": "10.1523/jneurosci.5779-12.2013",
        "label": "Shigetomi 2013 — Astrocyte TRPA1 channel deletion reduces basal Ca2+ and D-serine release, impairing NMDAR-dependent LTP",
        "value": "Qualitative: TRPA1(-/-) astrocytes show reduced basal Ca2+ and loss of constitutive D-serine release; NMDAR-dependent LTP is impaired",
        "direction": "decrease",
        "n_analyzed": null,
        "n_definition": "n not reported in abstract",
        "scope_region": "Mouse hippocampal CA1 acute slice",
        "taxonomic_level": "combined slice electrophysiology / imaging / biosensor",
        "scope_population": "Schaffer collateral → CA1 LTP; astrocyte basal Ca2+; extracellular D-serine",
        "value_source_sentence": "Using pharmacology, TRPA1(-/-) mice, imaging, electrophysiology, and D-serine biosensors, our data indicate that astrocyte TRPA1 channels contribute to basal Ca(2+) levels and are required for constitutive D-serine release into the extracellular space, which contributes to NMDA receptor-dependent LTP.",
        "numeric_value_qualitative": "reduced basal Ca2+ / reduced D-serine / impaired LTP"
      }
    ],
    "comparison_id": "FD1_astrocyte_ca2_LTP_and_coagonist",
    "interpretation": "Local, single-astrocyte Ca2+ clamp in individual CA1 astrocytes produces ~23% reduction of NMDAR-mediated fEPSPs that is rescued by exogenous D-serine (Henneberger 2010), and astrocyte-specific TRPA1 channel knockout abolishes constitutive D-serine release and impairs NMDAR-dependent LTP (Shigetomi 2013). In apparent contrast, global IP3R2 (Itpr2) genetic ablation yields no measurable change in either evoked synaptic transmission or plasticity (Petravicz/Agulhon 2008/2010). The reconciliation most consistent with these data is that multiple Ca2+-entry pathways (IP3R2-dependent somatic and IP3R2-independent perisynaptic/TRPA1 microdomain) contribute to gliotransmitter supply, and global IP3R2 ablation preserves the microdomain pathways that drive LTP-relevant D-serine release.",
    "homogeneity_check": {
      "same_metric_exact": false,
      "all_hippocampal_CA1": true,
      "comparability_caveats": "Three distinct astrocyte manipulations (single-cell Ca2+ clamp; IP3R2 genetic KO or MrgA1 overactivation; TRPA1 genetic KO) with different spatial scales of Ca2+ disruption. All assess hippocampal CA1 NMDAR-dependent plasticity/LTP, but Henneberger measures NMDAR fEPSP/EPSC change, Petravicz/Agulhon measure mEPSC/eEPSC/plasticity, and Shigetomi measures LTP + D-serine biosensor. n-definitions differ (slices vs. cells vs. mice). Comparability across these entries is at the level of \"hippocampal NMDAR-dependent plasticity under astrocyte Ca2+ perturbation\", not at the level of an identical quantitative metric.",
      "n_definition_consistent": false,
      "scope_region_consistent": true,
      "taxonomic_level_consistent": false,
      "scope_population_consistent": false
    }
  },
  "section_id": "section_04_evidence_package",
  "source_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes/blob/1a55da0634a3bc04e5688792ed12141ce271d28e/evidence/section_04_evidence_package.json",
  "target_ref": "wiki_page:computationalreviewastrocytes-04",
  "review_repo": "ComputationalReviewAstrocytes",
  "section_ref": "wiki_page:computationalreviewastrocytes-04",
  "source_path": "evidence/section_04_evidence_package.json",
  "source_refs": [
    "paper:paper-5525e0e4dcd1",
    "paper:paper-b422988f09f8",
    "paper:paper-bd699ea0aec5"
  ],
  "section_title": "Gliotransmission: Evidence and Controversy",
  "source_policy": {
    "mode": "public_source_pointer_with_short_context",
    "notes": [
      "Local review repositories are read-only inputs.",
      "SciDEX stores paper metadata, structured evidence, file pointers, and short citation contexts; it does not copy full review prose."
    ],
    "source_commit_sha": "1a55da0634a3bc04e5688792ed12141ce271d28e",
    "source_repository_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes"
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  "generation_status": "complete",
  "review_bundle_ref": "analysis_bundle:ab-029ee9411fe2",
  "origin_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes/blob/1a55da0634a3bc04e5688792ed12141ce271d28e/evidence/section_04_evidence_package.json",
  "commit_sha": "1a55da0634a3bc04e5688792ed12141ce271d28e",
  "created_by": "persona-jerome-lecoq-gbo-neuroscience",
  "repository_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes"
}