Projection-defined median raphe Pet+ subpopulations are diversely implicated in seizure

• DOI: 10.1016/j.nbd.2023.106358
• Publication Date: 2023-11-16T00:17:23Z
• Authors: Heming Cheng; Qiuwen Lou; Nanxi Lai; Liying Chen; Shuo Zhang; Fan Fei; Chenshu Gao; Shuangshuang Wu; Feng Han; Jinggen Liu; Yi Guo; Zhong Chen; Cenglin Xu; Yi Wang
• Keywords: Forebrain; Raphe; Raphe nuclei; Anterograde tracing; Dorsal raphe nucleus

The raphe nuclei, the primary resource of forebrain 5-HT, play an important but heterogeneous role in regulating subcortical excitabilities. Fundamental circuit organizations different median (MR) subsystems are far from completely understood. In present study, using cell-specific viral tracing, Ca2+ fiber photometry and epilepsy model, we map out efferent afferent MR Pet+ subpopulations their divergent roles epilepsy. We found that PetMR neurons send both collateral parallel innervations to downstream regions through subpopulations. Notably, CA3-projecting largely distinct habenula (Hb)-projecting anatomical distribution topological organization, while majority overlapped with medial septum (MS)-projecting Further, photometry, monitor activities hippocampal-kindling seizure, a classical model pathological mechanisms caused by excitation-inhibition imbalance. soma during periods generalized seizures. These contributed projection-defined subpopulations, manifesting as increased CA3 decreased activity Hb resulting upstream differences. Together, our findings provide novel framework showing topologically heterogenous connections diversely implicated This may help understanding nature 5-HTergic paradox systems