Investigation of functional and axonal plasticity in kisspeptin neurons following early social isolation in transgenic mice

In this study, it was investigated how the stress of social isolation in adolescence affects the functions and axonal projections of Kisspeptin neurons in the hypothalamic Arcuate Nucleus (ARC). For this purpose, the Kiss: Cre transgenic mouse line was used. On the post-natal 21st day (P21), the mice were placed in social isolation for 3 weeks. During this period, mice were living alone in opaque cages, while mice in the social group were kept alive in groups of three in normal cages. Locomotor activities, feeding behavior and anxiety of mice were observed after isolation. GFP-Adone Associated Virus (AAV) was injected into the hypothalamic ARC regions of mice to visualize the kisspeptin neurons. Electrophysiology was recorded from ARC Kisspeptin neurons of these mice. Axonal projections of ARC Kisspeptin neurons were viewed under the confocal microscop. Kisspeptin, NeurokininB and Dynorphine neuropeptides expression in the ARC region was examined using the immunofluorescence technique. Looking at the results obtained from the behavioral experiments, it was seen that females in the isolated group were more active than the other groups in the nocturnal phase (p <0.005), and the mice in the social group were more active than those in the isolated group. There was no significant difference in feeding behavior between the groups. Mice in the isolated group were found to be more anxious in the elevated plus maze test (p <0.05). It was observed that the action potential frequencies of ARC Kisspeptin neurons of mice in the social group were higher than the mice in the isolated group (p <0.001), and the action potential frequencies of female mice in the social group were higher than that of female and male mice in the isolated group (p <0.001). When the immunofluorescence results were examined, it was seen that the amount of Dynorphine in the ARC regions of the mice in the isolated group was higher than the social group (p <0.05). It was observed that the amount of Nerokinin B was higher in mice in the isolated group and the amount of Kisspeptin in mice in the social group, but statistical significance was not observed. When axonal projection analyzes were examined, a more intense projection of hypothalamic ARC Kisspeptin neurons in social group mice was observed to the Anteroventral Periventricular (AVPV) region compared to those in the isolated group. There was no difference between groups for ARC Kisspeptin axonal projections to other parts of the brain. According to these findings, it was observed that social isolation exposed during adolescence affected the locomotor and anxiety behavior of mice and suppressed the functions of Kisspeptin neurons.