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  1. Live 4ea7d28a1ce1
    5/17/2026, 4:45:12 PM
    Content snapshot
    {
      "kind": "infographic",
      "prompt": "Direct comparison of LTP/behavior outcomes across astrocyte Ca2+/gliotransmission perturbations reveals the field's central conflict: single-astrocyte or co-agonist manipulations produce large, replicable LTP effects (Henneberger 40-percentage-point drop; Adamsky +50% gain; D-cycloserine saturation gain), but global IP3R2 KO leaves plasticity-dependent behavior intact. The pattern is consistent with non-IP3R2 Ca2+ sources (TRPA1, mitochondria) being the relevant trigger for D-serine release.",
      "provider": "other",
      "raw_fields": {
        "papers": [
          {
            "doi": "10.1038/nature08673",
            "value": "52 → 12% fEPSP (control → depletion)",
            "method": "patch-clamped single astrocyte + extracellular fEPSP recording",
            "metric": "LTP magnitude (fEPSP % change) — control vs single-astrocyte D-serine depletion (within-study contrast)",
            "conditions": [
              {
                "n": 6,
                "value": "52 ± 11%",
                "ci_or_error": "±11% SEM",
                "n_definition": "slices",
                "condition_label": "control (astrocyte D-serine intact, HOAsp omitted)",
                "value_source_sentence": "Omitting HOAsp robustly induces LTP (52 ± 11%, n = 6, p = 0.0052; green)."
              },
              {
                "n": 7,
                "value": "12 ± 11%",
                "ci_or_error": "±11% SEM",
                "n_definition": "slices",
                "condition_label": "intra-astrocyte HOAsp (D-serine depleted in single patched astrocyte)",
                "value_source_sentence": "Intra-astrocyte HOAsp blocks induction of LTP (fEPSP change: +12 ± 11%, n = 7, p = 0.32; orange) following depletion of D-serine using HFS in APV; arrows, HFS onset."
              }
            ],
            "text_access": "fulltext",
            "scope_region": "hippocampus CA1",
            "study_system": "mouse acute hippocampal slice, CA3-CA1",
            "taxonomic_level": "fine type",
            "contrast_summary": "~40-percentage-point loss of LTP when D-serine is depleted from a single patched astrocyte in the local neuropil",
            "scope_population": "Schaffer collateral-CA1 synapses near patched astrocyte",
            "value_source_sentence": "Omitting HOAsp robustly induces LTP (52 ± 11%, n = 6, p = 0.0052; green). Intra-astrocyte HOAsp blocks induction of LTP (fEPSP change: +12 ± 11%, n = 7, p = 0.32; orange) following depletion of D-serine using HFS in APV.",
            "experimental_conditions": "single-astrocyte patch-load with/without HOAsp; HFS"
          },
          {
            "doi": "10.1038/s41398-023-02725-7",
            "value": "150.1% → 183.1% of baseline (control HFS → +DCS)",
            "method": "extracellular field EPSP recording",
            "metric": "LTP magnitude (% of baseline EPSP) — HFS alone vs HFS + D-cycloserine saturation (within-study contrast)",
            "conditions": [
              {
                "n": 8,
                "value": "150.1 ± 12.2% of baseline",
                "ci_or_error": "±12.2% SEM",
                "n_definition": "slices",
                "condition_label": "HFS in control solution",
                "value_source_sentence": "HFS in control solution induced significant LTP, to 150.1 ± 12.2% of the baseline ( n = 8, p = 0.0078 vs. the baseline)."
              },
              {
                "n": 8,
                "value": "183.1 ± 9.0% of baseline",
                "ci_or_error": "±9.0% SEM",
                "n_definition": "slices",
                "condition_label": "HFS + bath D-cycloserine (saturates NMDAR glycine site)",
                "value_source_sentence": "The addition of DCS to the bath solution significantly augmented LTP, to 183.1 ± 9.0% ( n = 8, p = 0.0078 vs. the baseline, p = 0.0464 vs. control HFS)."
              }
            ],
            "text_access": "fulltext",
            "scope_region": "hippocampus CA1",
            "study_system": "mouse acute hippocampal slice, CA1",
            "taxonomic_level": "fine type",
            "contrast_summary": "Saturating the NMDAR co-agonist site with exogenous D-cycloserine increases LTP magnitude by ~33 percentage points, implying endogenous co-agonist availability is sub-saturating in control conditions.",
            "scope_population": "Schaffer collateral-CA1 synapses",
            "value_source_sentence": "HFS in control solution induced significant LTP, to 150.1 ± 12.2% of the baseline ( n = 8); the addition of DCS to the bath solution significantly augmented LTP, to 183.1 ± 9.0% ( n = 8, p = 0.0464 vs. control HFS).",
            "experimental_conditions": "HFS ± bath D-cycloserine"
          },
          {
            "n": 0,
            "doi": "10.1016/j.cell.2018.05.002",
            "value": "~50% potentiation",
            "method": "patch-clamp EPSC recording",
            "metric": "Potentiation of EPSC amplitude by astrocyte Gq-DREADD activation during HFS",
            "n_analyzed": "cells across slices (not specified in sentence)",
            "ci_or_error": "F(19,190)=3.158, p<0.00005",
            "text_access": "fulltext",
            "n_definition": "cells",
            "scope_region": "hippocampus CA1",
            "study_system": "mouse acute hippocampal slice, CA1",
            "taxonomic_level": "fine type",
            "scope_population": "Schaffer collateral-CA1 synapses",
            "value_source_sentence": "Surprisingly, we observed a 50% potentiation of the EPSC amplitude in response to the same stimulus in GFAP::hM3Dq slices treated with CNO (crimson), but not in slices from the same mice exposed to ACSF (blue) only (time-by-treatment interaction F (19,190) = 3.158, p < 0.00005).",
            "experimental_conditions": "GFAP::hM3Dq Gq-DREADD + CNO during HFS-like stimulus"
          },
          {
            "n": 0,
            "doi": "10.3389/fnbeh.2014.00384",
            "value": "no detectable change",
            "method": "Morris water maze + other behavioral tests",
            "metric": "Effect of astrocyte IP3R2 knockout on behavioral correlate of plasticity (Morris water maze)",
            "n_analyzed": "not specified in sentence (cKO cohort)",
            "ci_or_error": null,
            "text_access": "fulltext",
            "n_definition": "animals",
            "scope_region": "hippocampus (MWM-dependent)",
            "study_system": "mouse, conditional IP3R2 KO, behavioral battery",
            "taxonomic_level": "broad category",
            "scope_population": "bulk plasticity-dependent learning",
            "value_source_sentence": "Morris water maze testing, a behavioral correlate of learning and memory, was unaffected by lack of astrocyte IP3R2-mediated Ca(2+)-signaling.",
            "experimental_conditions": "global/constitutive IP3R2 conditional knockout vs wild-type"
          }
        ],
        "comparison_id": "ltp-magnitude-astrocyte-manipulation",
        "comparison_name": "LTP magnitude across astrocyte Ca2+/gliotransmission manipulations in hippocampal CA1",
        "comparison_type": "cross-study conflict",
        "what_it_reveals": "Direct comparison of LTP/behavior outcomes across astrocyte Ca2+/gliotransmission perturbations reveals the field's central conflict: single-astrocyte or co-agonist manipulations produce large, replicable LTP effects (Henneberger 40-percentage-point drop; Adamsky +50% gain; D-cycloserine saturation gain), but global IP3R2 KO leaves plasticity-dependent behavior intact. The pattern is consistent with non-IP3R2 Ca2+ sources (TRPA1, mitochondria) being the relevant trigger for D-serine release.",
        "homogeneity_check": {
          "caveats": [
            "Hippocampal CA1 is common across all rows, but readouts differ (fEPSP slope vs EPSC amplitude vs behavioral proxy).",
            "Henneberger manipulates a single astrocyte; Agulhon 2014 manipulates the whole hippocampus genetically — single-cell vs global perturbations are not directly comparable.",
            "D-cycloserine saturates the NMDAR co-agonist site pharmacologically rather than manipulating the astrocyte, so it is a positive-control anchor rather than a replicate of astrocyte-specific manipulation.",
            "Adamsky Gq-DREADD activation is a gain-of-function probe; other rows are loss-of-function — directionality is explicitly opposite.",
            "Morris water maze score is a behavioral proxy for LTP, not LTP itself — inclusion is appropriate for testing behavioral consequence but not for direct slope comparison."
          ],
          "n_definition_uniform": "false",
          "scope_region_uniform": "true",
          "taxonomic_level_uniform": "false",
          "scope_population_uniform": "false"
        },
        "suggested_plot_type": "forest plot"
      },
      "section_id": "section_08_evidence_package",
      "source_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes/blob/1a55da0634a3bc04e5688792ed12141ce271d28e/evidence/section_08_evidence_package.json",
      "target_ref": "wiki_page:computationalreviewastrocytes-08",
      "review_repo": "ComputationalReviewAstrocytes",
      "section_ref": "wiki_page:computationalreviewastrocytes-08",
      "source_path": "evidence/section_08_evidence_package.json",
      "source_refs": [
        "paper:paper-0685af1d3f41",
        "paper:paper-5525e0e4dcd1",
        "paper:paper-79c338afafe0",
        "paper:paper-9c595c660d61"
      ],
      "section_title": "Astrocytes in Synaptic Plasticity",
      "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"
      },
      "generation_status": "complete",
      "review_bundle_ref": "analysis_bundle:ab-029ee9411fe2",
      "origin_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes/blob/1a55da0634a3bc04e5688792ed12141ce271d28e/evidence/section_08_evidence_package.json",
      "commit_sha": "1a55da0634a3bc04e5688792ed12141ce271d28e",
      "created_by": "persona-jerome-lecoq-gbo-neuroscience",
      "repository_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes"
    }