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

The dorsal raphe nucleus (DR) and median raphe nucleus (MR) contain populations of glutamatergic and GABAergic neurons regulating diverse behavioral functions. Their whole-brain input-output circuits remain incompletely understood. We used viral tracing combined with fluorescence micro-optical sectioning tomography to generate a comprehensive whole-brain atlas of inputs and outputs of glutamatergic and GABAergic neurons in the DR and MR. We discovered that these neurons receive inputs from similar upstream brain regions. The glutamatergic and GABAergic neurons in the same raphe nucleus have divergent projection patterns with differences in critical brain regions. Specifically, MR glutamatergic neurons project to the lateral habenula via multiple pathways. Correlation and cluster analysis indicated that glutamatergic and GABAergic neurons in the same raphe nucleus receive inputs from heterogeneous neurons in upstream brain regions and send different collateral projections. This connectivity atlas provides insights into the cell heterogeneity, anatomical connectivity and behavioral functions of the raphe nucleus.

Attenuation of stress-induced behavioral changes by activation of serotonin type 7 receptors in the median raphe nucleus of rats

Background: Exposure to stressful aversive situations induces physiological and behavioral changes. Serotonin has been suggested to mediate such changes, as well as adaptation to stressful events. Serotoninergic projections arising from the median raphe nucleus to the dorsal hippocampus have been suggested to promote adaptation to chronic aversive stimuli. Such pathway may involve serotonin type 1a receptor-mediated neurotransmission. However, the serotonin 7 receptor can also be found in the median raphe nucleus and may be involved in mechanisms underlying response to stress. Aims: In this work we sought to investigate if activation of serotonin type 7 receptors would attenuate stress-induced deficits in different animal models of depression. Methods: Male Wistar rats with a guide-cannula aimed to the median raphe nucleus were submitted to restraint or forced swim stress and were tested in an elevated plus maze or forced swim test, respectively, 24 h later. SB 258741 (serotonin type 7 receptor antagonist) and/or LP 44 (serotonin type 7 receptor agonist) were administered intra-median raphe nucleus immediately before or after exposure to stress or before test. Control groups received intra-median raphe nucleus treatment 24 h or immediately before test in the elevated plus maze or forced swim test. Results: LP 44 attenuated restraint-induced exploratory deficits independently of the moment it was administered. Similar results were observed in the forced swim test, with the exception on post-stress condition. These effects on adaptation to stress induced by serotonin type 7 receptor activation were prevented by previous treatment with SB 258741. Conclusions: Our data support the idea that activation of median raphe nucleus serotonin 7 receptor is important to the development of adaptation to stress.