scholarly journals Median raphe controls acquisition of negative experience in the mouse

Science ◽  
2019 ◽  
Vol 366 (6469) ◽  
pp. eaay8746 ◽  
Author(s):  
András Szőnyi ◽  
Krisztián Zichó ◽  
Albert M. Barth ◽  
Roland T. Gönczi ◽  
Dániel Schlingloff ◽  
...  

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.

2005 ◽  
Vol 94 (4) ◽  
pp. 2561-2574 ◽  
Author(s):  
Shaomin Li ◽  
Viktor Varga ◽  
Attila Sik ◽  
Bernat Kocsis

The median raphe nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expressed in the MRN by serotonergic and nonserotonergic cells, including GABAergic and glutamatergic neurons. This study investigated the mechanisms by which the fluctuating GABA tone in the MRN leads to induction or suppression of hippocampal theta rhythm. We found that MRN application of the GABAA agonist muscimol (0.05–1.0 mM) or GABAB agonist baclofen (0.2 mM) by reverse microdialysis had strong theta promoting effects. The GABAA antagonist bicuculline infused in low concentrations (0.1, 0.2 mM) eliminated theta rhythm. A short period of theta activity of higher than normal frequency preceded hippocampal desynchronization in 46% of rats. Bicuculline in larger concentrations (0.5, 1.0, 2.0 mM) resulted in a biphasic response of an initial short (<10 min) hippocampal desynchronization followed by stable theta rhythm that lasted as long as the infusion continued. The frequency and amplitude of theta waves were higher than in control recordings and the oscillations showed a conspicuous intermittent character. Hippocampal theta rhythm elicited by MRN administration of bicuculline could be completely (0.5 mM bicuculline) or partially (1.0 mM bicuculline) blocked by simultaneous infusion of the GABAB antagonist CGP35348 . Our findings suggest that the GABAergic network may have two opposing functions in the MRN: relieving the theta-generators from serotonergic inhibition and regulating the activity of a theta-promoting circuitry by the fluctuating GABA tone. The two mechanisms may be involved in different functions.


Hippocampus ◽  
2015 ◽  
Vol 26 (3) ◽  
pp. 289-300 ◽  
Author(s):  
Brian H. Bland ◽  
Cheryl E. Bland ◽  
M. Bruce MacIver

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jing Ren ◽  
Alina Isakova ◽  
Drew Friedmann ◽  
Jiawei Zeng ◽  
Sophie M Grutzner ◽  
...  

Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.


2002 ◽  
Vol 145 (3) ◽  
pp. 383-394 ◽  
Author(s):  
Gonzalo Viana Di Prisco ◽  
Zimbul Albo ◽  
Robert P. Vertes ◽  
Bernat Kocsis

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