Summary: Researchers have identified 34 distinct subtypes of medium spiny neurons (MSNs) in the nucleus accumbens, a brain region important for reward and addiction. The findings challenge the traditional view of MSNs as a homogenous group and reveal a complex diversity with potential implications for understanding addiction and developing targeted therapies. The study suggests that these findings may be conserved across species, providing insight into human brain function.
Key Facts:
34 different MSN subtypes have been identified, each with their own unique genetic profile. MSNs play an important role in reward processing and substance use disorders. This discovery may lead to more targeted and effective treatments for addiction.
Source: University of Pennsylvania
A research team co-led by the University of Pennsylvania School of Nursing has identified 34 distinct subtypes of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a key brain region involved in pleasure and motivation, marking a major advance in understanding the complex neural circuitry underlying reward and addiction.
The findings, published in Nature’s Scientific Reports, provide insight into the diversity of these neurons and their potential role in substance use disorders.
MSNs are the major neuron type in the NAc and have long been classified based on their expression of dopamine receptors, but this new study reveals a much more complex picture of MSN diversity.
By analysing a large dataset of single-nucleus RNA-seq data from rat brains, the researchers identified 34 distinct MSN subtypes, each with their own unique genetic profile.
“Our study challenges the traditional view of MSNs as a homogenous population,” said co-first author Heath D. Schmidt, PhD, professor in the Department of Biobehavioral Health Sciences at the University of Pennsylvania’s School of Nursing.
“By uncovering this level of diversity, we can begin to understand how specific MSN subtypes contribute to different aspects of reward processing and addiction.”
The researchers also found that these MSN subtypes are conserved across species, suggesting that this discovery could have broad implications for human brain function and behavior.
Additionally, by analyzing genetic data related to substance use disorders, the research team identified potential differences in the role of specific MSN subtypes in these diseases.
This groundbreaking research lays the foundation for future studies aimed at developing targeted therapies for addiction and other brain disorders. Understanding the specific functions of different MSN subtypes will enable scientists to develop treatments that precisely target these cells, potentially leading to more effective and less harmful interventions.
Funding: This work was supported in part by a Pennsylvania Department of Health Nonprescription Tobacco Reconciliation Act grant, Pharmacogenetics of Opioid Use Disorder, National Institutes of Health grants R01 DA037897, R21 DA045792, R21 DA 057458, R21 DA 055846, NIH/NIDA DP1DA054394, K01 AA028292, and R01 AA030056, Tobacco Related Disease Research Program (TRDRP) grant number T32IR5226, and Department of Veterans Affairs grant I01 BX004820. The investigators have no conflicts of interest to report.
About this Addiction and Genetics Research News
Author: Ed Federico
Source: University of Pennsylvania
Contact: Ed Federico – University of Pennsylvania
Image: This image is provided by Neuroscience News
Original research: Open Access.
“Single-nucleus transcriptome atlas of medium spiny neurons in the rat nucleus accumbens,” Heath Schmidt et al., Scientific Reports
Abstract
A single-nucleus transcriptome atlas of medium spiny neurons in the rat nucleus accumbens
The neural processing of rewarding stimuli involves several different regions, including the nucleus accumbens (NAc). The majority of neurons in the NAc are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by their expression of dopamine receptors, although there is evidence that a broader range of subtypes exists.
To investigate MSN heterogeneity, we analyzed single-nucleus RNA-seq data from the largest available rat NAc dataset.
Analysis of 48,040 NAc MSN nuclei identified major populations belonging to striosomes and matrix compartments. Integration with mouse and human data demonstrated consistency across species, and disease association scoring using results from genome-wide association studies revealed potentially distinct roles for MSN populations in substance use disorders.
Additional high-resolution clustering identified 34 transcriptomically distinct MSN subtypes that were definable by a limited number of marker genes.
These data demonstrate the diversity of MSNs in the NAc and provide a basis for more targeted genetic manipulation of specific populations.
