EPIC: region + neurotransmitter grouping classes for brain neurons #3788

Summary

We are preparing a release of the Whole Mouse Brain Ontology (WMBO, built from the Yao et al. 2023 whole mouse brain taxonomy, CCN20230722) that promotes ~450 transcriptomic types to CL. Before doing that, we tested how well current CL can classify them automatically from two properties: soma location and neurotransmitter.

Most brain-region × neurotransmitter grouping classes are missing from CL. Of the 239 neuronal types that need a direct CL parent, current CL places 64% under only a neurotransmitter class plus "central nervous system neuron". Adding the general grouping classes below would give 82% of them a single region + neurotransmitter parent.

This epic requests those classes. They all follow one pattern, so a DOSDP template is probably the right vehicle:

'<region> <NT> neuron'
EquivalentTo: '<NT> neuron' and 'has soma location' some <Uberon region>

The existing precedents are cerebellum glutamatergic neuron (CL:2000028) and midbrain dopaminergic neuron (CL:2000097). These are general classes, not mouse-specific.

How the evidence was gathered

• Location: the deepest brain region (Allen Mouse Brain Atlas structure, mapped to Uberon through the Uberon–MBA bridge) holding ≥ 80% of a type's cells in both MERFISH atlases, Yao 2023 and Zhuang 2023.
• Neurotransmitter: a neurotransmitter carried by every cluster in the type.
• Classification: each type was written as a defined class and classified against CL 2026-06-08 with ELK.
• Counts: "types" is the number of WMB types in the promotion set that would fall under the class; "anchors" is how many of those have no promoted parent and so need a direct CL parent.

Terms requested

Midbrain, hindbrain and cerebellum

• midbrain glutamatergic neuron: glutamatergic neuron ⊓ has soma location some midbrain (UBERON:0001891). 38 types, 28 anchors (e.g. APN C1ql2, PAG Pou4f1 Ebf2, SCig Foxb1 Otx2)
• midbrain GABAergic neuron: UBERON:0001891. 39 types, 20 anchors (e.g. SC-PAG Lef1 Emx2, SCs Pax7 Nfia)
• pons glutamatergic neuron: UBERON:0000988. 10 types, 8 anchors
• pons GABAergic neuron: UBERON:0000988. 14 types, 8 anchors
• pons serotonergic neuron: UBERON:0000988. 4 types (MB-MY Tph2 Glut-Sero supertypes). Consider whether existing raphe nuclei neuron (CL:0002610) should be its parent or sibling.
• medulla oblongata glutamatergic neuron: UBERON:0001896. 17 types, 14 anchors (e.g. MV-SPIV Slc6a2, SPVO Mafa Meis2)
• medulla oblongata GABA-Gly neuron: GABA-Gly neuron (CL:0008059) ⊓ soma in UBERON:0001896. 11 types, 9 anchors (e.g. MDRN Hoxb5 Ebf2, NTS-MDRNd Prox1 Zic1)
• hindbrain glutamatergic neuron: UBERON:0002028. 7 types; a parent for types spanning pons and medulla
• hindbrain GABA-Gly neuron: UBERON:0002028. 5 types
• brainstem glutamatergic neuron: UBERON:0002298. 9 types (see caveat 2)
• brainstem GABAergic neuron: UBERON:0002298. 15 types, 12 anchors (see caveat 2)
• cerebellum GABAergic neuron: UBERON:0002037. 15 types (Purkinje, MLI, PLI, Golgi). This would be a parent of Purkinje cell, molecular layer interneuron and similar.
• cerebellum GABA-Gly neuron: UBERON:0002037. 3 types (CBX Golgi, CB PLI Gly-Gaba)

Diencephalon

• hypothalamus glutamatergic neuron: UBERON:0001898. 24 types, 10 anchors (e.g. PVH-SO-PVa Otp, PMv-TMv Pitx2, MM Foxb1)
• hypothalamus GABAergic neuron: UBERON:0001898. 6 types
• Thalamic glutamatergic neurons: covered by existing thalamic excitatory neuron (CL:4023068), once its location axiom is fixed (separate bug ticket).

Telencephalon

• cerebral cortex glutamatergic neuron: UBERON:0000956. 7 types. A general parent for the IT/ET/CT/L6b glutamatergic cortical classes, which currently have no common glutamatergic + cortex parent.
• neocortex glutamatergic neuron: UBERON:0001950. 13 types
• hippocampal formation glutamatergic neuron: UBERON:0002421. 26 types, 14 anchors (CA, DG, subiculum, entorhinal, PPP). Would sit under existing hippocampal neuron (CL:0002608).
• cerebral cortex GABAergic neuron: UBERON:0000956. 9 types. Existing cerebral cortex GABAergic interneuron (CL:0010011) is interneuron-only.
• striatum GABAergic neuron: UBERON:0002435. 14 types. A parent of the medium spiny neurons and striatal interneurons.
• cerebral nuclei GABAergic neuron: UBERON:8440012. 5 types
• cerebral nuclei glutamatergic neuron: UBERON:8440012. 4 types
• cerebral nuclei cholinergic neuron: UBERON:8440012. 3 types (PAL-STR Gaba-Chol)
• telencephalon glutamatergic neuron: UBERON:0001893. 6 types (e.g. NLOT, MEA, PIR-ENTl types spanning several telencephalic divisions)
• olfactory bulb GABAergic neuron: UBERON:0002264. About 9 types (OB Trdn, OB Meis2 Thsd7b, OB Frmd7). Would sit above existing olfactory bulb interneuron (CL:1001434).
• olfactory bulb glutamatergic neuron: UBERON:0002264. About 4 types (OB Eomes Ms4a15)
• olfactory region GABAergic / glutamatergic neuron (editors: which Uberon class?). About 8 GABAergic and 6 glutamatergic types span the Allen "olfactory areas" (bulb plus AON, PIR, TT…). The bridge maps that division to UBERON:0002894 olfactory cortex, which may exclude the bulb.

Caveats

1. Counts are from mouse data, but the classes are general. The labels follow the existing <region> <NT> neuron pattern; editors may prefer adjectival forms ("hypothalamic", "pontine", "medullary").
2. "Brainstem" means different things in Allen and Uberon. The Allen atlas "brain stem" includes the interbrain (thalamus and hypothalamus); Uberon's brainstem (UBERON:0002298) does not. The brainstem requests are valid in the Uberon sense, but a few of the types counted here (e.g. STN, PH) are diencephalic and would classify elsewhere.
3. Optional region-only parents. "midbrain neuron", "pons neuron", "medulla oblongata neuron", "hindbrain neuron", "hypothalamus neuron" (only hypothalamus cell exists) and "cerebral nuclei neuron" don't exist. They aren't needed for these region + NT classes to classify, but they would complete the lattice alongside cerebral cortex neuron, striatum neuron and cerebellar neuron.
4. Related: Terms needed for Whole Mouse Brain  #2852 (terms needed for Whole Mouse Brain), Basal Ganglion product EPIC #3321 (Basal Ganglion product EPIC).