Identifying the Zincergic Innervation of the Basolateral Amygdala in a Novel Transgenic Mouse

Abstract

In the brain, zinc is sequestered into the vesicles of a subset of glutamatergic neurons by the protein Zinc Transporter 3 (ZnT3), encoded by the gene SLC30A3. This type of zinc, called “vesicular zinc”, is found primarily in the telencephalon, and acts as a neuromodulator at many receptors. Efforts to visualize vesicular zinc and assess its effects on behaviour have relied on methods such as selenium-based staining and ZnT3 knockout (KO) mice; however, these methods have important limitations that were unavoidable until the recent creation of a novel transgenic mouse model, the ZnT3cre/KO-mCherry (ZnT3cre) mouse. This model makes use of tamoxifen-inducible Cre found in all cells that contain ZnT3, which can then be targeted and modulated by viral vectors such as Adeno-Associated Viruses (AAVs). In addition, the KO of SLC30A3 can also be achieved with great temporal and spatial precision by way of Dre-expressing AAVs. This project aimed to be one of the first to characterize this model, using Cre-dependent, retrograde AAVs targeting the Basolateral Amygdala (BLA) to achieve Cre-dependent labelling of zincergic neurons. Cre-dependent labelling was identified in several afferents of the BLA including hippocampus, sensory regions, and cortical areas. The implications, limitations, and future directions of these results are discussed. This project provides foundational steps towards integrating the ZnT3cre mouse model into future research projects.