Endogenous oxytocin neuron projecting to the hippocampus participates in the modulation of cognitive behavior

Abstract

Previous reports suggested that the administration of oxytocin (OXT) modulates cognitive function, such as learning and memory. However, little is known about the role of endogenous OXT in cognitive function. To address this issue, we utilized Oxt-iCre (C57BL/6-Oxttm1.1(Cre)Ksak) mice and chemogenetic activation of OXT neurons by Cre-dependent transfection of DREADD, hM3Dq. Male Oxt-iCre mice were injected with AAV8-hSyn-DIO-hM3Dq-mCherry into the paraventricular nucleus of the hypothalamus (PVN). Then, we examined whether the specific activation of OXT neurons influences on working memory and long-term spatial memory in Y-maze and novel object recognition (NOR) tests. After the behavioral tests, the expression of c-Fos was examined. We identified the mCherry positive axons in the hippocampus. In addition, the administration of hM3Dq-specific agonist, Clozapine-N-oxide (CNO), significantly increased novel object preference in the NOR test, while no significant effect was observed in the Y-maze test. Further, the number of c-Fos positive neurons significantly increased in the dentate gyrus in the CNO-treated mice. These results suggested that the OXT neurons in the PVN project to the hippocampus and the endogenous OXT participates in the modulation of cognitive behavior in mice.