# CBLN2 promoter enables genetic access to wide-field neurons of the tree shrew superior colliculus

## TL;DR

Researchers developed a genetic tool using the CBLN2 promoter to target wide-field neurons in tree shrews and mice, revealing distinct input patterns in these neurons.

## Contribution

The first viral tool derived from the tree shrew genome for cell-type-specific targeting across species.

## Key findings

- CBLN2 is validated as a molecular marker for tree shrew wide-field neurons.
- AAVs based on the CBLN2 promoter enable selective targeting of wide-field neurons across species.
- Tree shrew wide-field neurons receive distinct excitatory inputs based on dendritic location.

## Abstract

Wide-field (WF) neurons of the tectopulvinar pathway integrate retinal and cortical inputs via large dendritic arbors crucial for rapid visual motion detection. Previous studies identified potential marker genes for mouse WF neurons. Here, we validate CBLN2 as a molecular marker of the tree shrew WF neurons and construct AAVs that exploit CBLN2 promoter to selectively target WF neurons across species. Using intersectional genetics in the tree shrew, we show that WF neuron dendrites receive a distinct pattern of VGluT1+ and VGluT2+ inputs based on their distance from the cell body in the dorsoventral axis of the superior colliculus (SC). This represents the first example of a viral tool derived from the tree shrew genome for cell-type-specific targeting across species. Our results provide a foundation for studying SC circuitry in higher-order mammals and for extending this approach to additional conserved cell types in the SC and other brain regions.

•CBLN2 marks wide-field (WF) neurons in the tree shrew superior colliculus•We develop cell-type-specific AAVs based on the tree shrew CBLN2 promoter•These tools enable labeling and manipulation of WF neurons across species•Tree shrew WF neurons are differentially innervated by distinct excitatory inputs

CBLN2 marks wide-field (WF) neurons in the tree shrew superior colliculus

We develop cell-type-specific AAVs based on the tree shrew CBLN2 promoter

These tools enable labeling and manipulation of WF neurons across species

Tree shrew WF neurons are differentially innervated by distinct excitatory inputs

The superior colliculus (SC) is an evolutionarily conserved midbrain structure, the function of which has adapted across species to meet specific sensory demands. Despite the conservation of cardinal SC cell types, our understanding of their contributions to behavior remains limited, in part due to a lack of cell-type-specific tools in higher-order mammals in which transgenic approaches are not feasible. To start addressing this gap, we devised a viral genetic approach to target one such cell type, termed the wide-field neurons, in the tree shrew and mouse.

Kipcak and Erisir use CBLN2-promoter-based AAVs to access wide-field (WF) neurons of the SC in a pre-primate species, the tree shrew, as well as in the mouse. Using intersectional genetics, they demonstrate that tree shrew WF neurons receive retinal and cortical excitatory inputs preferentially at distal or proximal dendrites in the SC.