# Dopaminergic Neurons in the Zebrafish Subpallium Belong to the Extended Medial Amygdala

**Authors:** Daniel Armbruster, Thomas Mueller, Wolfgang Driever

PMC · DOI: 10.1002/cne.70079 · 2025-08-05

## TL;DR

The study identifies a new region in zebrafish brains called the extended medial amygdala, which contains a group of dopamine-producing neurons.

## Contribution

The paper introduces a new subdivision of the zebrafish subpallium and identifies its role in forming the extended medial amygdala with heterogeneous dopaminergic neurons.

## Key findings

- The dorsalmost division of the ventral telencephalon (Vdd) is subdivided into Vdd1 and Vdd2, with Vdd2 forming the extended medial amygdala.
- Dopaminergic neurons in Vdd2 are part of the extended medial amygdala and show differential expression of calbindin2a and cortistatin/sst7.

## Abstract

The amygdala is a heterogeneous, multinuclear telencephalic structure critical for motivated and emotion‐related behaviors in vertebrates. In ray‐finned fish (Actinopterygii) like the teleost zebrafish, a telencephalic outward‐growing process called eversion makes defining amygdaloid territories particularly challenging. Teleosts are also peculiar in that they develop numerous dopaminergic (DA) neurons in the subpallium, while in tetrapods, such populations are less prominent or appear only transiently. To shed light on the organization of the amygdala in teleosts, we pursued an evolutionary developmental approach focusing on the topological origin of subpallial DA neurons. Specifically, we analyzed the distribution of tyrosine hydroxylase (Th) in conjunction with expression patterns of pax6a+b, isl1a, nkx2.1, lhx8a, otpa+b, and calb2a as markers of different telencephalic subdivisions in brains of 5‐ and 30‐day‐old zebrafish (Danio rerio, Teleostei). Our data show that the previously identified dorsalmost division of the ventral telencephalon (Vdd) needs to be subdivided into an anteroventral pax6a/b‐positive portion (Vdd1) and a posterodorsal pax6a/b‐negative portion (Vdd2). This pax6a‐negative Vdd2 portion develops into the extended medial amygdala (EMeA), including the DA population adjacent to the pallial–subpallial border. Our results also show that the EMeA DA neurons form a heterogeneous group of amygdaloid neurons because they differentially express calb2a and sst7. Our work sheds light on the early evolution and development of the amygdala and provides a foundation for functional analysis of the newly defined DA subtypes of the extended amygdala in zebrafish.

We identify directly adjacent to the pallial–subpallial boundary a pax6a‐negative dorsal Vdd2 portion of the zebrafish larval subpallium that develops into the extended medial amygdala (EMeA). Zebrafish subpallial dopaminergic neurons that locate to Vdd2 belong to the EMeA and form a heterogeneous group differentially expressing calbindin2a and cortistatin/sst7.

## Linked entities

- **Genes:** pax6a (paired box 6a) [NCBI Gene 30567], pax6b (paired box 6b) [NCBI Gene 60639], isl1a (ISL LIM homeobox 1a) [NCBI Gene 30147], NKX2-1 (NK2 homeobox 1) [NCBI Gene 7080], lhx8a (LIM homeobox 8a) [NCBI Gene 378959], otpa (orthopedia homeobox a) [NCBI Gene 560759], otpb (orthopedia homeobox b) [NCBI Gene 30316], calb2a (calbindin 2a) [NCBI Gene 393691], SST7 (somatostatin 7) [NCBI Gene 395106]
- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** th (tyrosine hydroxylase) [NCBI Gene 30384], ptdss2 (phosphatidylserine synthase 2) [NCBI Gene 100004136] {aka PSS-2}, pax6a (paired box 6a) [NCBI Gene 30567] {aka PAXZF-A, Pax6.1, cb280, fc20e07, pax-a, pax6}, dlx2a (distal-less homeobox 2a) [NCBI Gene 30574] {aka dlx-2, dlx2, zgc:110518}, otpb (orthopedia homeobox b) [NCBI Gene 30316] {aka cb977, otp, otp1}, calb2b (calbindin 2b) [NCBI Gene 393684] {aka calb2, wu:fq17g09, zgc:73099}, otpa (orthopedia homeobox a) [NCBI Gene 560759], calb1 (calbindin 1) [NCBI Gene 100001650] {aka fj53a05, wu:fj53a05}, nkx2.4b (NK2 homeobox 4b) [NCBI Gene 58112] {aka nk2.1a, nkx2.1, nkx2.1a, nkx2.4a, titf1, titf1a}, sst1.1 (somatostatin 1, tandem duplicate 1) [NCBI Gene 326018] {aka PPSS1, SS1, fd57e04, sst1, wu:fd57e04, zgc:92779}, lhx8a (LIM homeobox 8a) [NCBI Gene 378959] {aka cb875, fk78g12, lhx7, lhx8, wu:fk78g12}, gad1a (glutamate decarboxylase 1a) [NCBI Gene 100329827] {aka si:dkey-249g23.3}, pax6b (paired box 6b) [NCBI Gene 60639] {aka Pax6.2, cb566, fc09c10, id:ibd5095, wu:fc09c10, wu:fc33g08}, calb2a (calbindin 2a) [NCBI Gene 393691] {aka calb2l, wu:fq18e08, zgc:73115}, isl1a (ISL LIM homeobox 1a) [NCBI Gene 30147] {aka Isl-1, isl1, islet-1}, tbr1b (T-box brain transcription factor 1b) [NCBI Gene 58042] {aka tbr1}, lhx5 (LIM homeobox 5) [NCBI Gene 30465] {aka lim5}, th2 (tyrosine hydroxylase 2) [NCBI Gene 414844], sst6.1 (somatostatin family member 6.1) [NCBI Gene 751721] {aka PPSS3, SS2, cort, sst3, sst7, zgc:153708}, gad1b (glutamate decarboxylase 1b) [NCBI Gene 378441] {aka GAD67, gad1}
- **Diseases:** cardiac arrest (MESH:D006323), schizophrenia (MESH:D012559), social behavior deficits (MESH:D019958), addiction (MESH:D019966), depression (MESH:D003866)
- **Chemicals:** DNP (MESH:D019297), KCl (MESH:D011189), PFA (MESH:C003043), DMSO (MESH:D004121), Tween 20 (MESH:D011136), calcium (MESH:D002118), PBS (MESH:D007854), Agarose (MESH:D012685), methanol (MESH:D000432), TNT (MESH:D014303), formamide (MESH:C031066), NaCl (MESH:D012965), heparin (MESH:D006493), Glycerol (MESH:D005990), 5x (-), MS-222 (MESH:C003636), SCC (MESH:C007020), DA (MESH:D004298), HCl (MESH:D006851), Triton X-100 (MESH:D017830), Digoxigenin (MESH:D004076), hydrogen peroxide (MESH:D006861)
- **Species:** Carassius auratus (goldfish, species) [taxon 7957], Danio rerio (leopard danio, species) [taxon 7955], Cyprinus carpio (carp, species) [taxon 7962], Pelophylax ridibundus (European green frog, species) [taxon 8406], Mus musculus (house mouse, species) [taxon 10090], Xenopus laevis (African clawed frog, species) [taxon 8355], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** NM_131149 — Bos taurus (Bovine), Finite cell line (CVCL_3074)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12324066/full.md

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Source: https://tomesphere.com/paper/PMC12324066