Regulatory effects of median raphe GABAergic and dopaminergic neurons on social behavior and reinforcement- based learning
Tiago Chaves Do Carmo
János Szentágothai Neurosciences
Dr. Bereczki Dániel
2025-11-17 14:00:00
Neuroendocrinology
Dr. Fekete Csaba
Dr. Zelena Dóra Dr. Varga Viktor
Dr. Zachar Gergely
Dr. Varró Petra
Dr. Gyires Klára
Dr. Herbert-Minkó Krisztina
Dr. Fekete Csaba
We investigated the roles of GABAergic and dopaminergic neurons in the MRR in modulating behaviors relevant to neuropsychiatric disorders. Using chemogenetics and behavioral testing, we dissected the specific contributions of these neuronal subtypes to reinforcement-based learning, social behavior, anxiety, and memory.
Project I. examined VGAT-MRR neurons in reinforcement-based learning (VGAT-Cre mice, DREADDs). Specific GABAergic neuron manipulation yielded more pronounced behavioral changes than nonspecific MRR stimulation, suggesting roles in response disinhibition and aversive learning.
Project II. focused on VGAT-MRR neurons in social behavior and anxiety (VGAT-Cre mice). Stimulation enhanced social investigation, while inhibition had no effect. A mild anxiogenic effect was observed with inhibition, but no effects on short-term social or working memory were found.
Project III. investigated DAT-MRR neuron function, confirming their presence in mice and humans. Chemogenetic manipulation revealed specific effects on social behavior: stimulation decreased social investigation, while inhibition increased prosocial interactions. No effects were seen on locomotion, anxiety, or memory. IHC confirmed viral expression, neuronal phenotype, and c-Fos activation.
These findings highlight distinct, context-dependent roles for VGAT-MRR and dopaminergic neurons. While chemogenetics allows cell-type specificity, limitations regarding temporal precision and off-target effects warrant consideration. The observed behavioral effects suggest the MRR is a critical node in relevant neural circuits, warranting further investigation using techniques like optogenetics and electrophysiology, combined with detailed anatomical and functional mapping.
