Compromised mammillary body connectivity and psychotic symptoms in mice with di- and mesencephalic ablation of ST8SIA2

• DOI: 10.1038/s41398-022-01816-1
• Publication Date: 2022-02-03T08:03:35Z
• Authors: Melike Küçükerden; Ute E. Schuster; Iris Röckle; Gonzalo Alvarez-B...; Kerstin Schwabe; Herbert Hildebrandt
• Keywords: Mammillary body; Fornix

Abstract Altered long-range connectivity is a common finding across neurodevelopmental psychiatric disorders, but causes and consequences are not well understood. Genetic variation in ST8SIA2 has been associated with schizophrenia, autism, bipolar disorder, St8sia2 −/− mice show number of related behavioral phenotypes. In the present study, we use conditional knockout (cKO) to dissect defects deficiency cortical interneurons, their environment, or di- mesencephalon. Neither separate nor combined diencephalic ablation caused disturbed thalamus-cortex observed mice. However, reproduced hypoplasia corpus callosum fornix mesencephalic displayed smaller mammillary bodies prominent loss parvalbumin-positive projection neurons size reductions mammillothalamic tract. addition, mammillotegmental tract peduncle, forming reciprocal connections between Gudden’s tegmental nuclei, as ventral nucleus were affected. Only these deficits enhanced MK-801-induced locomotor activity, exacerbated impairment prepulse inhibition response apomorphine, hypoanxiety elevated plus maze. We therefore propose that compromised body connectivity, independent from hippocampal input, leads psychotic-like responses -deficient