From Drug Target Review
Prior to their latest study, Jeremy Day, from the Department of Neurobiology at the University of Alabama at Birmingham, explained that the technologies available for research had held this understanding back. His research focused on one of the circuits linked to substance abuse, the NAc.
“One of the issues is that this is a very heterogeneous brain region with many different cell types and trying to define how those contribute differently to the various aspects of substance abuse has traditionally been a challenge. More recently, single-cell RNA sequencing tools have become available – these allow us to profile at a transcriptional level the cells of this region in a way that captures their heterogeneity, so we can understand how the cells are different from each other and how each may contribute to addiction.”
However, single-cell or single-nucleus sequencing only yields an estimation of what genes might be contributing to a symptom. To confirm the prediction, scientists have to complete a mechanistic study.
“For this we need to be able to express a gene or reporter molecule in an animal model to observe the impact, in my lab we use CRISPR to manipulate cells in vivo. I think the combination of single-cell sequencing technologies and CRISPR have given us traction to define what addiction looks like in these brain reward circuits.”