Interaction between 5-HT2A and D1/D5 receptors signalling in the retrosplenial cortex during recognition memory consolidation

The retrosplenial cortex (RSC) is particularly sensitive to changes that occur in mild cognitive impairment and Alzheimer's disease, making it crucial to understand the neuromodulatory systems that support its function. The RSC has been widely related to spatial and contextual memory, and also integrates sensory information into recognition memories, and previous work from our lab showed that both dopaminergic and serotonergic signalling in the RSC are required for object recognition (OR) memory consolidation. D1/D5 receptor activation reverses the amnesia induced by the ventral tegmental area inactivation, and 5-HT2A receptors (5-HT2AR) critically modulate OR memory processing. In this study, our aim was to analyze how these two systems interact in the RSC during memory processing. Thus, we used the Y-OR task combined with localized bilateral co-infusion into the RSC of SKF38393, a selective D1/D5 receptor agonist, and MDL, a selective 5-HT2AR antagonist, immediately after training and tested 24 h after. This co-infusion reversed the memory deficit induced by 5-HT2AR blockade. Conversely, 5-HT2AR agonist TCB-2 reversed the deficit induced by D1/D5 blockade with SCH23390, showing that activation of either system compensates for inhibition of the other. Together, these results show that dopaminergic and serotonergic signalling interact functionally in the RSC during recognition memory consolidation, supporting a model of crosstalk between these two neuromodulatory systems.