PT  - JOURNAL ARTICLE
AU  - Lucian Medrihan
AU  - Margarete Knudsen
AU  - Tatiana Ferraro
AU  - Pedro Del Cioppo Vasques
AU  - Yevgeniy Romin
AU  - Sho Fujisawa
AU  - Paul Greengard
AU  - Ana Milosevic
TI  - Glutamatergic projections from ventral hippocampus to nucleus accumbens cholinergic neurons are altered in a mouse model of depression
AID  - 10.1101/2022.04.20.488950
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.04.20.488950
4099  - http://biorxiv.org/content/early/2022/04/20/2022.04.20.488950.short
4100  - http://biorxiv.org/content/early/2022/04/20/2022.04.20.488950.full
AB  - The cholinergic interneurons (ChATs) of the nucleus accumbens (NAc) have a critical role in the activity of this region, specifically in the context of major depressive disorder. To understand the circuitry regulating this behavior we sought to determine the areas that directly project to these cells/interneurons by utilizing the monosynaptic cell-specific tracing technique. Mapping showed monosynaptic projections that are exclusive to NAc ChATs. To determine if some of these projections are altered in a depression mouse model, we used mice that do not express the calcium binding protein p11 specifically in ChATs (ChAT-p11 cKO) and display a depressive-like phenotype. Our data demonstrated that while the overall projection areas remain similar between wild type and in ChAT-p11 cKO mice, the number of projections coming from the ventral hippocampus (vHIP) is significantly reduced in the ChAT-p11 cKO mice. Furthermore, using optogenetics and electrophysiology we showed that glutamatergic projections from vHIP to NAc ChATs are severely altered in mutant mice. These results show that specific alterations in the circuitry of the accumbal ChAT interneurons could play an important role in the regulation of depressive-like behavior, reward seeking behavior in addictions, or psychiatric symptoms in neurodegenerative diseases.Competing Interest StatementThe authors have declared no competing interest.