MEDIAN RAPHE CONTROLS NEGATIVE EXPERIENCE: THE BEHAVIORAL EVIDENCE
Krisztián Zichó1, András Szőnyi1, Albert Barth1, Roland Gönczi1, Katalin E. Sos1, 2, Viktor Varga1, Tamás F. Freund1, Gábor Nyiri1
1 Laboratory of Cerebral Cortex Research, Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
2 János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary
Acquisition of negative experience is essential for the survival. Negative stimuli immediately and simultaneously activate the main aversive centers, the lateral habenula (LHb) and medial ventral tegmental area (mVTA) and the memory processing septo-hippocampal system. However, it is still unknown, which neurons coordinate these processes during negative experience. Here, we found that the brainstem median raphe region (MRR) harbors a new type of excitatory population of neurons that expresses vesicular glutamate transporter 2 (vGluT2). These neurons innervate LHb, mVTA and the septo-hippocampal system and they receive inputs from negative experience-related brain centers. MRR vGluT2 neurons are rapidly and selectively activated during aversive, but not rewarding events. Optogenetic stimulation of MRR vGluT2 neurons induced acute and conditioned place aversion, suppressed reward seeking behavior and created memory acquisition-promoting hippocampal theta-oscillations. By contrast, optogenetic inhibition of MRR vGluT2-neurons during an aversive foot-shock impaired both contextual and cued fear memory-formation and prevented fear generalization. Our results suggest that MRR vGluT2-neurons are both necessary and sufficient to acquire negative experience and they may play an important role in several types of mood disorders.