A research team – co-led by Penn Nursing – has made a significant breakthrough in understanding the complex neural circuitry underlying reward and addiction by identifying 34 distinct subtypes of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a key brain region involved in pleasure and motivation. The findings, published in the journal Scientific Reports by Nature, offer insights into the diversity of these neurons and their potential roles in substance use disorders.
MSNs are the primary type of neuron in the NAc and have long been classified based on their expression of dopamine receptors. However, this new research reveals a far more intricate picture of MSN diversity. By analyzing a massive dataset of single-nucleus RNA sequencing data from rat brains, the researchers identified 34 distinct MSN subtypes, each with its own unique genetic profile.
“Our study challenges the traditional view of MSNs as a homogenous population,” said co-lead author Heath D. Schmidt, PhD, Professor in Penn Nursing’s Department of Biobehavioral Health Sciences. “By uncovering this level of diversity, we can begin to understand how specific MSN subtypes contribute to different aspects of reward processing and addiction.”
Clustering of snRNA-seq data
Single nucleus RNA sequencing was performed on nucleus accumbens samples from male, drug-naïve Brown Norway rats and data were clustered based on transcriptomic profile. (a) Uniform manifold approximation and projection (UMAP) dimension reduction plot with nuclei colored by major cell type. Normalized expression of two MSN marker genes (Bcl11b and Pde10a) is visualized by both violin plot (b) and scatter plot (c). (d–k) Feature plots display expression of markers for major glial populations and non-MSN neuronal subtypes for cluster identification.
The researchers also found that these MSN subtypes are conserved across species, suggesting that the findings may have broad implications for human brain function and behavior. Additionally, by analyzing genetic data linked to substance use disorders, the team identified potential differences in the roles of specific MSN subtypes in these conditions.
This groundbreaking research provides a foundation for future studies aimed at developing targeted therapies for addiction and other brain disorders. By understanding the specific functions of different MSN subtypes, scientists can develop treatments that precisely target these cells, potentially leading to more effective and less harmful interventions.
Source – Penn Nursing