Median raphe controls acquisition of negative experience in the mouse

András Szo, Krisztián Zichó, Albert M. Barth, Roland T. Gönczi, Dániel Schlingloff, Bibiána Török, Eszter Sipos, Abel Major, Zsuzsanna Bardóczi, Katalin E. Sos, Attila I. Gulyás, Viktor Varga, Dóra Zelena, Tamás F. Freund, Gábor Nyiri

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Abstract

Adverse events need to be quickly evaluated and memorized, yet how these processes are coordinated is poorly understood. We discovered a large population of excitatory neurons in mouse median raphe region (MRR) expressing vesicular glutamate transporter 2 (vGluT2) that received inputs from several negative experience–related brain centers, projected to the main aversion centers, and activated the septohippocampal system pivotal for learning of adverse events. These neurons were selectively activated by aversive but not rewarding stimuli. Their stimulation induced place aversion, aggression, depression-related anhedonia, and suppression of reward-seeking behavior and memory acquisition–promoting hippocampal theta oscillations. By contrast, their suppression impaired both contextual and cued fear memory formation. These results suggest that MRR vGluT2 neurons are crucial for the acquisition of negative experiences and may play a central role in depression-related mood disorders.

Original languageEnglish
Article numbereaay8746
JournalScience
Volume366
Issue number6469
DOIs
Publication statusPublished - Nov 29 2019

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Szo, A., Zichó, K., Barth, A. M., Gönczi, R. T., Schlingloff, D., Török, B., Sipos, E., Major, A., Bardóczi, Z., Sos, K. E., Gulyás, A. I., Varga, V., Zelena, D., Freund, T. F., & Nyiri, G. (2019). Median raphe controls acquisition of negative experience in the mouse. Science, 366(6469), [eaay8746]. https://doi.org/10.1126/science.aay8746