THE REUNIENS NUCLEUS OF THE THALAMUS: THE CORNERSTONE OF BEHAVIORAL FLEXIBILITY AND SPATIAL MEMORY CONSOLIDATION IN RATS

Numerous neurological and neuropsychiatric disorders, including Alzheimer’s disease, anxiety, depression, schizophrenia, and post-traumatic stress disorder, are associated with dysfunction of the thalamic reuniens nucleus. This midline thalamic structure is strategically positioned to mediate reciprocal interactions between the hippocampus and the medial prefrontal cortex (mPFC), a network critically involved in memory and cognitive flexibility. Accumulating evidence indicates that functional coupling between the mPFC and the reuniens supports adaptive behavior by coordinating hippocampal-dependent spatial representations with prefrontal executive demands. Consistent with this framework, our previous work showed that lesions or pharmacogenetic inactivation of the reuniens nucleus impair flexible spatial navigation in the double H-maze and disrupt systems consolidation of spatial and fear memories. Together, these findings support an integrative role for the reuniens nucleus in optimizing cortico-hippocampal information flow in response to environmental demands. In the present study, we used a chemogenetic DREADD approach in adult Long-Evans rats to investigate the functional directionality of mPFC–reuniens circuitry during early spatial memory processing and cognitive flexibility. We selectively targeted mPFC neurons projecting to the reuniens nucleus and reuniens neurons projecting to the mPFC. By combining spatial navigation and object-in-place recognition tasks, we tested for a double dissociation between this bidirectional pathway. This supports cognitive operations that extend beyond hippocampal interactions, highlighting a broader role for midline thalamic circuits in the executive control of memory.