NEURAL MECHANISMS OF SPATIAL CHOICE: DCA1 PLASTICITY, CUE PROCESSING & BEHAVIORAL VARIABILITY

Hippocampal synaptic plasticity, in particular long-term potentiation (LTP), has long been considered a central mechanism underlying spatial memory. However, recent evidence from studies in genetically modified mice has challenged this concept, proposing instead that hippocampal plasticity may play a role in spatial decision-making (Bannerman et al., 2012).

To examine the molecular and behavioural determinants of spatial choice, we designed a fully automated behavioural platform that enables continuous tracking of mouse locomotion and navigation. The system comprises three interconnected corridors outfitted with video monitoring, visual and auditory cue modules, automated doors, and liquid reward delivery, allowing animals to explore freely while acquiring rewards.

Using this paradigm, we assessed spatial decision-making in male and female C57BL/6 mice and observed no sex differences in overall performance. We systematically evaluated the contributions of motivational state, cue modality, reward distance, and dorsal CA1 (dCA1) synaptic plasticity. Plasticity was disrupted via lentiviral shRNA-mediated knockdown of the synaptic scaffold protein PSD-95.

Food restriction enhanced motivation, learning efficiency, and choice dynamics, while closer reward placement accelerated acquisition. Cue manipulations in males showed that removal of visual cues impaired performance. PSD-95-dependent dCA1 plasticity emerged as a key regulator of attentional engagement and decision-making strategies.

Notably, animals could be segregated into high-, intermediate-, and low-performing subgroups, indicating inherent differences in decision strategies. To further investigate the neural correlates underlying performance variability between groups, whole-brain c-Fos immunostaining across serial sections was performed.

Collectively, these results elucidate how hippocampal plasticity, environmental information, and individual variability interact to shape spatial decision-making.