| First Author | Cheng H | Year | 2023 |
| Journal | Neurobiol Dis | Volume | 189 |
| Pages | 106358 | PubMed ID | 37977434 |
| Mgi Jnum | J:342893 | Mgi Id | MGI:7561332 |
| Doi | 10.1016/j.nbd.2023.106358 | Citation | Cheng H, et al. (2023) Projection-defined median raphe Pet(+) subpopulations are diversely implicated in seizure. Neurobiol Dis 189:106358 |
| abstractText | The raphe nuclei, the primary resource of forebrain 5-HT, play an important but heterogeneous role in regulating subcortical excitabilities. Fundamental circuit organizations of different median raphe (MR) subsystems are far from completely understood. In the present study, using cell-specific viral tracing, Ca(2+) fiber photometry and epilepsy model, we map out the forebrain efferent and afferent of different MR Pet(+) subpopulations and their divergent roles in epilepsy. We found that Pet(MR) neurons send both collateral and parallel innervations to different downstream regions through different subpopulations. Notably, CA3-projecting Pet(MR) subpopulations are largely distinct from habenula (Hb)-projecting Pet(MR) subpopulations in anatomical distribution and topological organization, while majority of the CA3-projecting Pet(MR) subpopulations are overlapped with the medial septum (MS)-projecting Pet(MR) subpopulations. Further, using Ca(2+) fiber photometry, we monitor activities of Pet(MR) neurons in hippocampal-kindling seizure, a classical epilepsy model with pathological mechanisms caused by excitation-inhibition imbalance. We found that soma activities of Pet(MR) neurons are heterogeneous during different periods of generalized seizures. These divergent activities are contributed by different projection-defined Pet(MR) subpopulations, manifesting as increased activities in CA3 but decreased activity in Hb resulting from their upstream differences. Together, our findings provide a novel framework of MR subsystems showing that projection-defined MR Pet(+) subpopulations are topologically heterogenous with divergent circuit connections and are diversely implicated in seizures. This may help in the understanding of heterogeneous nature of MR 5-HTergic subsystems and the paradox roles of 5-HTergic systems in epilepsy. |
