Investigating prefronto-striatal circuit dynamics during flexible decision-making

Cognitive flexibility is critical for enabling humans and animals to maintain and maximize rewarding outcomes in a changing environment, and often compromised in various psychiatric conditions including Schizophrenia (Lotus Thai, et al, 2019; Zhu, Ho-wai So, et al, 2021). Prefrontal cortex (PFC) and basal ganglia (BG) are both important brain systems in establishing and switching between flexible goal-directed strategies, and repetitive behaviours (Merre, et al, 2018; Hart, Balleine et al, 2014). The direct anatomical connection between PFC and striatum (STR; the input nucleus of BG) is considerable, up to 45% of layer 5 neurons from certain PFC-regions project to this structure (Gabbott, Busby, 2005). But how prefronto-striatal circuits communicate in goal-directed behaviour, and how relevant information is transmitted between these structures, is not well understood. First AAV based anterograde tracing was used to assess fine scale projection patterns between different prefrontal and striatal macro- and micro-domains. Building on a newly in-house developed behavioural platform, we present a head-fixed mouse probabilistic decision-making paradigm for investigating response-outcome association based behavioural flexibility in wild-type and psychiatric disease associated mouse strains. Using this approach we identify PFC neuronal representations essential for optimal task performance, in high channel count silicon probe recordings. We utilize optogenetic axonal projection tagging to test how information routing diverges from functionally, genetically or topologically defined prefrontal neuron populations to multiple striatal macro- and micro-domains. Our next steps are to compare behavioural metrics, and prefronto-striatal neuronal population dynamics between a well established genetic mouse model for schizophrenic risk and wild-type littermates.