Add new term: hippocampal trilaminar cell (CL:9900000) by ai4c-agent[bot] · Pull Request #3745 · obophenotype/cell-ontology

ai4c-agent · 2026-09-11T09:25:46Z

Summary

Adds a new CL term hippocampal trilaminar cell (CL:9900000), per issue #3744.

The term describes a GABAergic interneuron of hippocampal CA1 with soma at the stratum oriens/alveus border, whose local axon distributes across strata oriens, pyramidale and radiatum (the arrangement for which the type is named) and which additionally projects to the subiculum.

Parents

hippocampal interneuron (CL:1001569)
GABAergic interneuron (CL:0011005)

Logical axioms

has soma location some CA1 stratum oriens (UBERON:0014552)
capable of some gamma-aminobutyric acid secretion, neurotransmission (GO:0061534)
sends synaptic output to region some CA1 stratum oriens (UBERON:0014552)
sends synaptic output to region some pyramidal layer of CA1 (UBERON:0014548)
sends synaptic output to region some CA1 stratum radiatum (UBERON:0014554)
sends synaptic output to region some subiculum (UBERON:0002191)

Synonyms

trilaminar cell (exact, PMID:7472426)
CA1 trilaminar cell (exact)
mGluR8a-innervated GABAergic trilaminar cell (related, PMID:32016558)

Following @dosumis' review of issue #3744

The tentative netrin-G1 expresses axiom has been omitted (the marker is not part of the description).
The muscarinic M2 acetylcholine receptor (CHRM2) expresses axiom has been omitted pending resolution of the correct PRO identifier. @dosumis - would you be able to advise on a suitable PR term (or a workaround) so this axiom can be added in a follow-up?

References cited on the term

PMID:7472426 (Sik et al. 1995) — original definition
PMID:16280590 (Ferraguti et al. 2005) — M2/mGluR8/subiculum projection
PMID:32016558 (Katona et al. 2020) — molecular profile and in vivo firing

Closes #3744

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Agent harness: claude-code
Triggered by: @ct31-sanger
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@dosumis

Creates a new CL term for the hippocampal trilaminar cell, a GABAergic interneuron of CA1 with soma at the stratum oriens/alveus border and a local axon that distributes across strata oriens, pyramidale and radiatum, additionally projecting to the subiculum. Per @dosumis' review on issue #3744, the tentative netrin-G1 'expresses' axiom has been omitted (marker not mentioned in the definition), and the muscarinic M2 acetylcholine receptor 'expresses' axiom has been omitted pending resolution of the correct PRO identifier. Parents: - hippocampal interneuron (CL:1001569) - GABAergic interneuron (CL:0011005) Logical axioms: - has soma location some CA1 stratum oriens (UBERON:0014552) - capable of some GABAergic neurotransmission (GO:0061534) - sends synaptic output to region some CA1 stratum oriens (UBERON:0014552) - sends synaptic output to region some pyramidal layer of CA1 (UBERON:0014548) - sends synaptic output to region some CA1 stratum radiatum (UBERON:0014554) - sends synaptic output to region some subiculum (UBERON:0002191) References: PMID:7472426, PMID:16280590, PMID:32016558 Closes #3744 Co-Authored-By: Claude Opus 4.7 <noreply@anthropic.com>

@dosumis

…01614) to CL:9900000 Adds the previously deferred `expresses` axiom for the muscarinic M2 acetylcholine receptor (PR:000001614) to hippocampal trilaminar cell (CL:9900000), per @dosumis' resolution of the correct PR identifier on issue #3744. Includes a Declaration for PR_000001614 (first use in CL). Axiom references: PMID:16280590 (Ferraguti et al. 2005) and PMID:32016558 (Katona et al. 2020), both of which document strong somato-dendritic M2 in this cell type. Note: PR imports may need updating so this term resolves during release. Co-Authored-By: Claude Opus 4.7 <noreply@anthropic.com>

ct31-sanger · 2026-09-16T13:14:00Z

#gogoeditdiff

github-actions · 2026-09-16T13:20:39Z

Here's a diff of how these changes impact the classified ontology (on -base file):

Ontology comparison

Left

Ontology IRI: http://purl.obolibrary.org/obo/cl/cl-base.owl
Version IRI: http://purl.obolibrary.org/obo/cl/releases/2026-09-16/cl-base.owl
Loaded from: file:/__w/cell-ontology/cell-ontology/src/ontology/cl-base-master.owl/cl-base.owl

Right

Ontology IRI: http://purl.obolibrary.org/obo/cl/cl-base.owl
Version IRI: http://purl.obolibrary.org/obo/cl/releases/2026-09-16/cl-base.owl
Loaded from: file:/__w/cell-ontology/cell-ontology/src/ontology/cl-base-pr.owl/cl-base.owl

Ontology imports

Ontology annotations

PR_000001614 `http://purl.obolibrary.org/obo/PR_000001614`

Added

Class: PR_000001614

RO_0013003 `http://purl.obolibrary.org/obo/RO_0013003`

Added

ObjectProperty: RO_0013003

UBERON_0002191 `http://purl.obolibrary.org/obo/UBERON_0002191`

Added

Class: UBERON_0002191

hippocampal trilaminar cell `http://purl.obolibrary.org/obo/CL_9900000`

Added

Class: hippocampal trilaminar cell
hippocampal trilaminar cell IAO_0000233 "CL new term request: hippocampal trilaminar cell #3744"
hippocampal trilaminar cell contributor 0000-0002-5507-2103
hippocampal trilaminar cell creator "Claude"
hippocampal trilaminar cell date "2026-09-11T09:21:23Z"^^dateTime
hippocampal trilaminar cell hasExactSynonym "CA1 trilaminar cell"
hippocampal trilaminar cell IAO_0000115 "A GABAergic interneuron of hippocampal CA1, with soma at the stratum oriens/alveus border. Its dendrites are largely confined to stratum oriens while its local axon distributes across strata oriens, pyramidale and radiatum - the arrangement for which the type is named - and it additionally projects to the subiculum. It expresses a high level of somato-dendritic muscarinic M2 acetylcholine receptor and lacks somatostatin, parvalbumin, vasoactive intestinal peptide, neuropeptide Y and calbindin. Its presynaptic inputs are unusually densely decorated with mGluR8a-containing terminals. Output synapses are strongly biased toward other interneurons, including parvalbumin-expressing cells, while also contacting pyramidal cell somata. Firing falls during movement and rises in prolonged bursts above 200 Hz during slow-wave sleep."
- hasDbXref "PMID:7472426"
- hasDbXref "PMID:32016558"
- hasDbXref "PMID:16280590"
hippocampal trilaminar cell hasRelatedSynonym "mGluR8a-innervated GABAergic trilaminar cell"
- hasDbXref "PMID:32016558"
hippocampal trilaminar cell hasExactSynonym "trilaminar cell"
- hasDbXref "PMID:7472426"
hippocampal trilaminar cell label "hippocampal trilaminar cell"
hippocampal trilaminar cell SubClassOf GABAergic interneuron
hippocampal trilaminar cell SubClassOf hippocampal interneuron
hippocampal trilaminar cell SubClassOf RO_0002100 some UBERON_0014552
hippocampal trilaminar cell SubClassOf RO_0013003 some UBERON_0002191
hippocampal trilaminar cell SubClassOf RO_0013003 some UBERON_0014548
hippocampal trilaminar cell SubClassOf RO_0013003 some UBERON_0014552
hippocampal trilaminar cell SubClassOf RO_0013003 some UBERON_0014554
hippocampal trilaminar cell SubClassOf RO_0002292 some PR_000001614
- hasDbXref "PMID:32016558"
- hasDbXref "PMID:16280590"

github-actions · 2026-09-16T13:20:43Z

Here's a diff of your edit file (unreasoned)

Ontology comparison

Left

Ontology IRI: http://purl.obolibrary.org/obo/cl.owl
Version IRI: None
Loaded from: file:/__w/cell-ontology/cell-ontology/master/src/ontology/cl-edit.owl

Right

Ontology IRI: http://purl.obolibrary.org/obo/cl.owl
Version IRI: None
Loaded from: file:/__w/cell-ontology/cell-ontology/branch/src/ontology/cl-edit.owl

Ontology imports

Ontology annotations

hippocampal trilaminar cell `http://purl.obolibrary.org/obo/CL_9900000`

Added

Class: hippocampal trilaminar cell
hippocampal trilaminar cell term tracker item "CL new term request: hippocampal trilaminar cell #3744"
hippocampal trilaminar cell contributor 0000-0002-5507-2103
hippocampal trilaminar cell creator "Claude"
hippocampal trilaminar cell date "2026-09-11T09:21:23Z"^^dateTime
hippocampal trilaminar cell has exact synonym "CA1 trilaminar cell"
hippocampal trilaminar cell definition "A GABAergic interneuron of hippocampal CA1, with soma at the stratum oriens/alveus border. Its dendrites are largely confined to stratum oriens while its local axon distributes across strata oriens, pyramidale and radiatum - the arrangement for which the type is named - and it additionally projects to the subiculum. It expresses a high level of somato-dendritic muscarinic M2 acetylcholine receptor and lacks somatostatin, parvalbumin, vasoactive intestinal peptide, neuropeptide Y and calbindin. Its presynaptic inputs are unusually densely decorated with mGluR8a-containing terminals. Output synapses are strongly biased toward other interneurons, including parvalbumin-expressing cells, while also contacting pyramidal cell somata. Firing falls during movement and rises in prolonged bursts above 200 Hz during slow-wave sleep."
- has cross-reference "PMID:16280590"
- has cross-reference "PMID:32016558"
- has cross-reference "PMID:7472426"
hippocampal trilaminar cell has_related_synonym "mGluR8a-innervated GABAergic trilaminar cell"
- has cross-reference "PMID:32016558"
hippocampal trilaminar cell has exact synonym "trilaminar cell"
- has cross-reference "PMID:7472426"
hippocampal trilaminar cell label "hippocampal trilaminar cell"
hippocampal trilaminar cell SubClassOf GABAergic interneuron
hippocampal trilaminar cell SubClassOf hippocampal interneuron
hippocampal trilaminar cell SubClassOf has soma location some CA1 stratum oriens
hippocampal trilaminar cell SubClassOf capable of some gamma-aminobutyric acid secretion, neurotransmission
hippocampal trilaminar cell SubClassOf RO_0013003 some subiculum
hippocampal trilaminar cell SubClassOf RO_0013003 some pyramidal layer of CA1
hippocampal trilaminar cell SubClassOf RO_0013003 some CA1 stratum oriens
hippocampal trilaminar cell SubClassOf RO_0013003 some CA1 stratum radiatum
hippocampal trilaminar cell SubClassOf expresses some muscarinic acetylcholine receptor M2
- has cross-reference "PMID:16280590"
- has cross-reference "PMID:32016558"

muscarinic acetylcholine receptor M2 `http://purl.obolibrary.org/obo/PR_000001614`

Added

Class: muscarinic acetylcholine receptor M2

ct31-sanger · 2026-09-16T13:27:51Z

Updated branch to have new PR term for muscarinic M2 acetylcholine receptor. The references and classes make logical sense. @ai4c-agent please update using available PR term PR:000001614.

ai4c-agent · 2026-09-16T13:28:07Z

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ai4c-agent · 2026-09-16T13:32:39Z

The expresses some PR:000001614 axiom is already on the branch — it was added in commit ea2801d ("Add expresses axiom for muscarinic M2 acetylcholine receptor (PR:000001614) to CL:9900000"). The reasoned/unreasoned diff bots have picked it up in their most recent runs.

Current axiom on CL:9900000:

SubClassOf(
  Annotation(oboInOwl:hasDbXref "PMID:16280590")
  Annotation(oboInOwl:hasDbXref "PMID:32016558")
  obo:CL_9900000
  ObjectSomeValuesFrom(obo:RO_0002292 obo:PR_000001614)
)

PR:000001614 is also present in src/ontology/imports/pr_terms.txt (added on master via #3746) and the branch has been merged with master, so the term resolves as muscarinic acetylcholine receptor M2 at release. No further edits are required.

🤖 Generated by @ai4c-agent

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Agent harness: claude-code
Triggered by: @ct31-sanger
Run: View workflow run

dosumis · 2026-09-16T13:35:55Z

/clara

github-actions · 2026-09-16T13:38:00Z

Claude Code is working…

I'll analyze this and get back to you.

View job run

dosumis · 2026-09-16T13:39:08Z

Looks good. Running one last check with Clara.

github-actions · 2026-09-16T15:10:18Z

Claude finished @dosumis's task in 8m 29s —— View job

CLARA routed-target verification — CL:9900000 (hippocampal trilaminar cell)

Load routing payload and group targets by term_id
Decompose ntr textual + relationship changes into atomic assertions
Convert synonym targets into atomic assertions
Stage B/C verification for each assertion
Write runs/CL_9900000/verdicts.json, tool_calls.jsonl, report.md
Post summary

Term-level result: PASS — 26/27 core assertions pass, 1 uncertain, 0 fail. No background assertions.

Tooling note: mcp__Asta_semanticscholar__snippet_search (the Stage B tool named in clara_workflow_ref/clara_workflow/agent_instructions.md) isn't available in this environment, so verification went straight to full-text/abstract evidence (get_europepmc_full_text for PMID:32016558; get_europepmc_paper_by_id abstracts for PMID:7472426 and PMID:16280590, whose full text wasn't retrievable). This is logged as a deviation_note in tool_calls.jsonl.

Findings:

All 16 decomposed definition claims, all 9 relationship-change claims (subclass, soma location, GABA capability, 4× synaptic-output-region, expresses PR:000001614), and both synonyms are directly supported by the cited literature (Sik et al. 1995, Ferraguti et al. 2005, Katona et al. 2020) — including the "mGluR8a-innervated GABAergic trilaminar cell" synonym, which is verbatim in PMID:32016558's title.
Uncertain: "lacks parvalbumin." None of the three cited references explicitly states the trilaminar cell itself is parvalbumin-negative — the closest supporting text says parvalbumin-positive interneurons are frequent postsynaptic targets of trilaminar cells (a different claim), plus an analogous mouse scRNA-seq cluster described as "lacking Sst or Pvalb." Worth a source check or a wording softener.
Minor evidence-source note (not a failure): "contacts pyramidal cell somata" is supported by Ferraguti et al. 2005's abstract, but Katona et al. 2020's own EM data describes contacts onto pyramidal cell dendritic shafts rather than somata — flagged for awareness only.

Full assertion-by-assertion detail: runs/CL_9900000/report.md, runs/CL_9900000/verdicts.json, runs/CL_9900000/tool_calls.jsonl.

Per the task's constraints, no ontology source files were edited and no commits/pushes/PRs were made — only the runs/CL_9900000/ output bundle was written.

github-actions · 2026-09-16T15:19:05Z

CLARA review for PR #3745

Base SHA: e5bce66aef6807ef1e62e1f90e333eee904a9ecc
Head SHA: d051acd21b3751b9c7fffdb9e59b77e45500ec05
Terms touched: 2
Total extracted changes: 20
Reviewable changes: 13
Decomposable changes: 1
Routed validation targets: 3
Routed NTR bundles: 1
Routed relationship targets: 0
Routed synonym targets with refs: 2

Stage 2/3 verification ran for 1 routed term(s).

Routed verification results

CL_9900000 — hippocampal trilaminar cell: UNCERTAIN (core: 27, fail: 0, uncertain: 1, background warnings: 0)

Currently ignored by routing

Existing-term text changes not yet routed: 0
Synonym changes without refs: 1

Artifacts uploaded:

changes.json
routing.json
runs/

dosumis · 2026-09-17T08:45:12Z

@ct31-sanger - I think look into this some more:

Uncertain: "lacks parvalbumin." None of the three cited references explicitly states the trilaminar cell itself is parvalbumin-negative — the closest supporting text says parvalbumin-positive interneurons are frequent postsynaptic targets of trilaminar cells (a different claim), plus an analogous mouse scRNA-seq cluster described as "lacking Sst or Pvalb." Worth a source check or a wording softener.

Note: "verification went straight to full-text/abstract evidence (get_europepmc_full_text for PMID:32016558; get_europepmc_paper_by_id abstracts for PMID:7472426 and PMID:16280590, whose full text wasn't retrievable)"

This suggests worth checking full test of PMID:7472426 and PMID:16280590 for any statements about pvalb.

ct31-sanger · 2026-09-17T09:26:14Z

I have checked PMID:7472426 and PMID:16280590 for any statements about pvalb/lack of parvalbumin in trilaminar cell. Neither references have evidence to support this. However, recent paper (June 2026) PMID:42268975 does support this claim by reporting that trilaminar cells lack parvalbumin (Pvalb) expression. @ai4c-agent please use this updated reference (PMID:42268975) to support claim.

ai4c-agent · 2026-09-17T09:26:30Z

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@ct31-sanger

Adds PMID:42268975 (Li et al. 2026, Sci Adv) as an additional xref on the definition of hippocampal trilaminar cell (CL:9900000), supporting the "lacks parvalbumin" claim that CLARA verification flagged as uncertain. The paper explicitly states of the Chrm2+ trilaminar IN cluster: "These INs have molecular characteristics of hippocampal trilaminar INs, including high expression of Chrm2 while lacking expression of Sst and Pvalb." Per @ct31-sanger's request on PR #3745. Co-Authored-By: Claude Opus 4.7 <noreply@anthropic.com>

ai4c-agent · 2026-09-17T09:31:06Z

Added PMID:42268975 (Li et al. 2026, Sci Adv, "Single-nucleus profiling reveals a core disease signature and cell type-specific vulnerabilities in early Rett syndrome") as an additional definition xref on CL:9900000 in commit 337e210.

The paper directly supports the "lacks parvalbumin" claim. From the Discussion:

"These INs have molecular characteristics of hippocampal trilaminar INs, including high expression of Chrm2 while lacking expression of Sst and Pvalb (54), consistent with a previous study that profiled different subclasses of CA1 inhibitory neurons (66)."

The definition xref list on the term is now PMID:7472426, PMID:16280590, PMID:32016558, PMID:42268975. No other axioms were changed.

🤖 Generated by @ai4c-agent

Model: claude-opus-4-7
Agent harness: claude-code
Triggered by: @ct31-sanger
Run: View workflow run

ct31-sanger · 2026-09-17T09:34:16Z

/clara

github-actions · 2026-09-17T09:36:41Z

Claude finished @ct31-sanger's task in 5m 10s —— View job

CLARA routed-target verification — CL:9900000 (hippocampal trilaminar cell)

Re-ran CLARA per @dosumis' /clara request, now that commit 337e210 added PMID:42268975 as support for the "lacks parvalbumin" claim.

Load routing payload and group targets by term_id
Decompose ntr textual + relationship changes into atomic assertions
Convert synonym targets into atomic assertions
Stage B/C verification for each assertion
Write runs/CL_9900000/verdicts.json, tool_calls.jsonl, report.md
Post summary

Term-level result: PASS — 27/27 core assertions pass, 0 uncertain, 0 fail. No background assertions.

Tooling note: as in the previous run, mcp__Asta_semanticscholar__snippet_search isn't available in this environment, so verification went straight to full-text/abstract evidence (get_europepmc_full_text for PMID:32016558 and PMID:42268975; get_europepmc_paper_by_id abstracts for PMID:7472426 and PMID:16280590, whose full text wasn't retrievable). Logged as a deviation_note in tool_calls.jsonl.

What changed since the last pass: the previously uncertain assertion — "lacks parvalbumin" — now resolves to pass. PMID:42268975 (Li et al. 2026) states in its Discussion:

"we identified this highly affected population as trilaminar INs, characterized by high expression of cholinergic receptor muscarinic 2 (Chrm2) while lacking expression of somatostatin (Sst), parvalbumin (Pvalb), and other IN subtype markers"

This directly supports the claim, closing the gap @dosumis and @ct31-sanger identified.

All other 26 assertions (definition claims, subclass/relationship axioms, and both synonyms) remain supported as in the prior pass, including the minor note that Katona et al. 2020's own EM data describes pyramidal-cell targets as dendritic shafts rather than somata (kept as pass since Ferraguti et al. 2005 explicitly states "pyramidal cell somata," per the any-reference-supports rule).

Full assertion-by-assertion detail: runs/CL_9900000/report.md, runs/CL_9900000/verdicts.json, runs/CL_9900000/tool_calls.jsonl.

Per the task's constraints, no ontology source files were edited and no commits/pushes/PRs were made — only the runs/CL_9900000/ output bundle was written.

github-actions · 2026-09-17T09:42:09Z

CLARA review for PR #3745

Base SHA: e5bce66aef6807ef1e62e1f90e333eee904a9ecc
Head SHA: 337e21040d6f6bf583b6b7fdf74fe4322e4f9310
Terms touched: 2
Total extracted changes: 20
Reviewable changes: 13
Decomposable changes: 1
Routed validation targets: 3
Routed NTR bundles: 1
Routed relationship targets: 0
Routed synonym targets with refs: 2

Stage 2/3 verification ran for 1 routed term(s).

Routed verification results

CL_9900000 — hippocampal trilaminar cell: PASS (core: 27, fail: 0, uncertain: 0, background warnings: 0)

Currently ignored by routing

Existing-term text changes not yet routed: 0
Synonym changes without refs: 1

Artifacts uploaded:

changes.json
routing.json
runs/

ai4c-agent Bot mentioned this pull request Sep 11, 2026

CL new term request: hippocampal trilaminar cell #3744

Closed

github-actions Bot and others added 2 commits September 11, 2026 10:46

Merge branch 'master' into ai4c-agent-issue-3744-run772

d051acd

ct31-sanger assigned dosumis Sep 16, 2026

Merge branch 'master' into ai4c-agent-issue-3744-run772

338886b

dosumis approved these changes Sep 17, 2026

View reviewed changes

dosumis merged commit deec919 into master Sep 18, 2026
3 checks passed

dosumis deleted the ai4c-agent-issue-3744-run772 branch September 18, 2026 07:14

Conversation

ai4c-agent Bot commented Sep 11, 2026

Summary

Parents

Logical axioms

Synonyms

Following @dosumis' review of issue #3744

References cited on the term

Uh oh!

ct31-sanger commented Sep 16, 2026

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github-actions Bot commented Sep 16, 2026

Ontology comparison

Left

Right

Ontology imports

Ontology annotations

PR_000001614 http://purl.obolibrary.org/obo/PR_000001614

Added

RO_0013003 http://purl.obolibrary.org/obo/RO_0013003

Added

UBERON_0002191 http://purl.obolibrary.org/obo/UBERON_0002191

Added

hippocampal trilaminar cell http://purl.obolibrary.org/obo/CL_9900000

Added

Uh oh!

github-actions Bot commented Sep 16, 2026

Ontology comparison

Left

Right

Ontology imports

Ontology annotations

hippocampal trilaminar cell http://purl.obolibrary.org/obo/CL_9900000

Added

muscarinic acetylcholine receptor M2 http://purl.obolibrary.org/obo/PR_000001614

Added

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ct31-sanger commented Sep 16, 2026

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ai4c-agent Bot commented Sep 16, 2026

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ai4c-agent Bot commented Sep 16, 2026

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dosumis commented Sep 16, 2026

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dosumis commented Sep 16, 2026

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CLARA routed-target verification — CL:9900000 (hippocampal trilaminar cell)

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github-actions Bot commented Sep 16, 2026

CLARA review for PR #3745

Routed verification results

Currently ignored by routing

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dosumis commented Sep 17, 2026

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ct31-sanger commented Sep 17, 2026

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ct31-sanger commented Sep 17, 2026

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CLARA routed-target verification — CL:9900000 (hippocampal trilaminar cell)

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github-actions Bot commented Sep 17, 2026

CLARA review for PR #3745

Routed verification results

Currently ignored by routing

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Reviewers

Assignees

PR_000001614 `http://purl.obolibrary.org/obo/PR_000001614`

RO_0013003 `http://purl.obolibrary.org/obo/RO_0013003`

UBERON_0002191 `http://purl.obolibrary.org/obo/UBERON_0002191`

hippocampal trilaminar cell `http://purl.obolibrary.org/obo/CL_9900000`

hippocampal trilaminar cell `http://purl.obolibrary.org/obo/CL_9900000`

muscarinic acetylcholine receptor M2 `http://purl.obolibrary.org/obo/PR_000001614`

github-actions Bot commented Sep 16, 2026 •

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