BEHAVIOURAL ALTERATIONS OF NOVEL OBJECT RECOGNITION IN A VALPROATE-INDUCED MOUSE MODEL OF AUTISM

The prenatal valproate (VPA) exposure-induced rodent model of autism replicates cognitive symptoms observed in autism spectrum disorder (ASD). The affected animals exhibit perseverative and stereotyped behaviours, decreased exploratory activity and memory deficits, combined with increased anxiety.
In our study, we aim to assess mechanisms underlying altered cognitive processing in VPA-treated mice in comparison with age-matched controls. We focus our investigations on the dorsal hippocampus, a brain centre for spatial navigation, learning and memory.
Swiss mice used in our experiments were exposed to VPA prenatally, having their mothers receiving a single dose of 400 mg/kg sodium-VPA intraperitoneal injection at gestational day 12.5. Mothers of controls were injected with saline (Sal). The offspring were pre-screened for ultrasound vocalisation, mechanical allodynia and sociability. Using VPA-treated and control mice, we conducted a hippocampus-dependent continuous novel object recognition (cNOR) task (Gava et al, 2024). For 2D tracking and analysis we used DeepLabCut (Mathis et al, 2018) and Matlab.
Our results show that during free open-arena exploration, VPA-treated mice spent more time in the centre 50% of the arena than the controls. Encountering 4 novel objects, in the last 5 minutes of the 15-min long sampling sessions (as the objects in the arena became more familiar), control mice spent less time with object exploration and the number of object exploration events also decreased. In contrast, VPA-treated mice did not show these novelty-related changes.
As a next step, we are extending our investigations studying neuromodulatory changes underlying these differences between VPA and Sal groups using fiber photometry.