FIRING PATTERNS AND OSCILLATIONS IN PREFRONTAL–HIPPOCAMPAL CIRCUITS IN A NOVEL STRATEGY-SWITCHING TASK FOR MICE NAVIGATING A VIRTUAL REALITY LINEAR MAZE

Synaptic plasticity and reorganization of spatial representations in the CA1 region of the rodent dorsal hippocampus (dHPC) are essential for learning and finding reward locations in familiar environments. In contrast, acquiring non-spatial cue-reward associations requires no dHPC at all. Thus, adjusting circuit operations and plasticity mechanisms, and rebalancing weights of inputs to the dHPC may be essential when shifting between spatial and non-spatial strategies to solve a task. Suggesting a top-down regulatory role for the medial prefrontal cortex (mPFC) its inactivation disrupts behavioral adaptation during such contingency shifts, but the underlying circuit mechanisms and the role of temporal coordination between the mPFC and the dHPC remain poorly understood. We train head-fixed mice in a novel virtual reality task where switches between spatial and cue-guided strategies are required to obtain rewards. To assess adaptations in circuit dynamics, we record local field potentials and action potentials of multiple single-units from the mPFC and the CA1 area of the dHPC as mice experience within-session rule changes for the first time. Preliminary results suggest that mice respond to rule switches by adjusting behavioral strategy, requiring progressively fewer trials across sessions to do so. Although no direct projections between the mPFC and dHPC were detected, viral tracing experiments identified the nucleus reuniens of the thalamus as a potential relay mediating top-down signals from the mPFC to the dHPC. Our findings may uncover mechanisms of cognitive flexibility, a capacity impaired in neurodevelopmental disorders such as schizophrenia and autism. Funded by FWF (Austria), grant P37089-B.