Major depressive disorder (MDD) affects ~5% of the global population and is a leading cause of disability. It is characterized by symptoms such as reduced motivation, heightened responses to negative experiences, social withdrawal, and anhedonia. However, patients differ widely in symptom profiles and recovery trajectories, and fewer than half respond effectively to current treatments. This highlights a critical need to better understand the biological mechanisms underlying depression.

Although several brain regions are known to be affected in MDD, the contribution of specific neuronal populations remains unclear. This gap is particularly relevant given the high cellular diversity within these regions, which may help explain differences in individual vulnerability and treatment response.

The nucleus accumbens (NAc), a key region involved in motivation and reward processing, has been strongly implicated in depression. Traditionally, its neurons are classified into two main types based on dopamine receptor expression (D1 and D2). However, emerging evidence—including our own findings—shows that these neurons are highly heterogeneous, with distinct subpopulations present in both healthy and depressive states.

DynamicDep aims to identify and characterize these neuronal subpopulations and their roles in depression-related behaviors, including resilience and susceptibility, in both sexes. Using advanced techniques such as spatial transcriptomics, calcium imaging, and optogenetics in clinically relevant animal models, this project seeks to uncover the neural circuit mechanisms underlying depression and support the development of more targeted therapies.