Median raphe controls acquisition of negative experience in the mouse

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.

Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in mouse dorsal and median raphe nucleus

“…However, there were no projections from DR glutamatergic and GABAergic neurons and scarce projections from MR GABAergic neurons to the LH, only MR glutamatergic neurons sent strong projections to the LH (mainly assembled in the medial part of LH) ( Figure 4B (Szőnyi et al, 2019), which supported the reliability of this projection pattern. The specific reciprocal connections between MR glutamatergic neurons and the LH suggested that MR glutamatergic neurons might be involved in some specific functions related to the LH.…”

“…The dorsal raphe nucleus (DR) and median raphe nucleus (MR) are important modulatory centers involved in a multitude of functions (Domonkos et al,2016;Huang et al, 2019;Szőnyi et al, 2019). They are implicated to have different and even antagonistic roles in the regulation of specific functions, such as emotional behavior, social behavior and aggression (Balázsfi et al, 2018;Ohmura et al, 2020;Teissier et al, 2015).…”

“…CC-BY 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted December 15, 2020. ; https://doi.org/10.1101/2020.12.15.422858 doi: bioRxiv preprint 3 MR, glutamatergic neurons are critical for processing negative experiences, and activation of them could induce aversive behavior, aggression and depressive symptoms (Szőnyi et al, 2019).…”

“…And MR glutamatergic neurons are innervated by certain aversion/fear or memory-related areas, such as the LH, and they innervate the LH, medial ventral tegmental area, medial septum and the vertical limbs of the diagonal bands of Broca (Szőnyi et al, 2019). Nevertheless, there is still a lack of whole-brain quantitative results and comprehensive analysis of the input-output circuits of glutamatergic and GABAergic neurons in the DR and MR.…”

Phenomenal Consciousness and Emergence: Eliminating the Explanatory Gap

“…In vertebrates, for instance, visual information is extensively processed in the retina, thalamus, parts of the cerebrum, and optic tectum; and in arthropods in the retina, lamina, medulla, lobula and central complex of the brain (Strausfeld, 2012;Feinberg and Mallatt, 2016a). As another illustration of extreme regional specialization, the core of the vertebrate brain has elaborated a dizzying number of centers for affective (emotional) consciousness: the habenula, basal forebrain, periaqueductal gray, parts of the reticular formation and more (Figure 3; Berridge and Kringelbach, 2015;Feinberg and Mallatt, 2016a;Hu, 2016;Feinberg and Mallatt, 2018a;Siciliano et al, 2019;Szõnyi et al, 2019).…”