Defining morphologically and genetically distinct GABAergic/cholinergic amacrine cell subtypes in the vertebrate retina

PLoS Biol. 2024 Feb 16;22(2):e3002506. doi: 10.1371/journal.pbio.3002506. eCollection 2024 Feb.

Abstract

In mammals, retinal direction selectivity originates from GABAergic/cholinergic amacrine cells (ACs) specifically expressing the sox2 gene. However, the cellular diversity of GABAergic/cholinergic ACs of other vertebrate species remains largely unexplored. Here, we identified 2 morphologically and genetically distinct GABAergic/cholinergic AC types in zebrafish, a previously undescribed bhlhe22+ type and a mammalian counterpart sox2+ type. Notably, while sole sox2 disruption removed sox2+ type, the codisruption of bhlhe22 and bhlhe23 was required to remove bhlhe22+ type. Also, both types significantly differed in dendritic arbors, lamination, and soma position. Furthermore, in vivo two-photon calcium imaging and the behavior assay suggested the direction selectivity of both AC types. Nevertheless, the 2 types showed preferential responses to moving bars of different sizes. Thus, our findings provide new cellular diversity and functional characteristics of GABAergic/cholinergic ACs in the vertebrate retina.

MeSH terms

  • Amacrine Cells* / metabolism
  • Animals
  • Cholinergic Agents / metabolism
  • Mammals
  • Retina / metabolism
  • Transcription Factors / metabolism
  • Zebrafish*

Substances

  • Cholinergic Agents
  • Transcription Factors

Grants and funding

This study was funded by grants from the National Key Research and Development Program of China (2020YFA0112700 to JH), grants STI2030-Major Projects(2021ZD0204500 to JH), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05 to JH), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32000000 to JH), the National Natural Science Foundation of China (31871035 to JH), and the State Key Laboratory of Neuroscience(to JH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.