Paired associates learning performance in rats requires the nucleus reuniens.

Abstract

Hospitalizations and deaths related to mental health disorders have increased in recent decades, highlighting the need for improved understanding of the neurocircuitry underlying cognitive dysfunction. Dysfunction in neural coordination between the hippocampus (HPC) and prefrontal cortex (PFC) is widely reported to be a signature of many mental health disorders. This circuit is crucial for many forms of adaptive behavior, with the nucleus reuniens (RE) of the thalamus hypothesized to be a critical hub that coordinates HPC-PFC interactions in the service of cognition. This study examined the role of the RE in associative memory by assessing the impact of its inactivation in male and female rats performing the Paired Associates Learning task, a touchscreen-based visuospatial memory paradigm with translational relevance for human mental health disorders. Using muscimol inactivation, we found that RE suppression significantly impaired Paired Associates Learning performance, supporting its role in HPC-PFC circuit coordination. Modulating nicotinic receptors in the RE with an agonist also produced significant deficits; however, we did not see any significant behavioral effects with an antagonist. These findings suggest that the RE is critical for Paired Associates Learning task performance, and its functional contribution may be modulated by cholinergic nicotinic signaling, but additional studies are necessary to test the robustness of this observation. Understanding RE's role in cognition may inform therapeutic strategies for psychiatric and neurological disorders characterized by HPC-PFC dysfunction. (PsycInfo Database Record (c) 2026 APA, all rights reserved).