The granular retrosplenial cortex is necessary in male rats for object-location associative learning and memory, but not spatial working memory or visual discrimination and reversal, in the touchscreen operant chamber

The retrosplenial cortex (RSC) is a hub of diverse afferent and efferent projections thought to be involved in associative learning. RSC shows early pathology in mild cognitive impairment (MCI) and Alzheimer's disease (AD), which impairs associative learning. To understand and develop therapies for diseases such as AD, animal models are essential. Given the importance of human RSC in object-location associative learning and the success of object-location associative paradigms in human studies and in the clinic, it would be of considerable value to establish a translational model of object-location learning for the rodent. For this reason, we sought to test the role of RSC in object-location learning in male rats using the object-location paired-associates learning (PAL) touchscreen task. First, increased cFos immunoreactivity was observed in granular RSC following PAL training when compared to extended pretraining controls. Following this, RSC lesions following PAL acquisition were used to explore the necessity of the RSC in object-location associative learning and memory, and two tasks involving only one modality: trial-unique nonmatching-to-location (TUNL) for spatial working memory and pairwise visual discrimination and reversal (PVD/PVR). RSC lesions impaired both memory for learned paired-associates, and learning of new object-location associations, but did not affect performance in either the spatial or visual single-modality tasks. These findings provide evidence that RSC is necessary for object-location learning and less so for learning and memory involving the individual modalities therein. Animal models are essential to understand and develop therapies for diseases such as Alzheimer's disease (AD). Given the importance of human retrosplenial cortex (RSC) in object-location associative learning and the success of these paradigms in human studies and in the clinic, it is of considerable value to establish a translational model of object-location learning for the rodent. We determined that lesions of the RSC in male rats following object-location paired-associates learning led to impairments in object-location associative memory and new learning but did not affect performance on tasks of the individual modalities (i.e. spatial and visual). These findings further validate the touchscreen PAL test as a viable translational test for modelling diseases, such as AD, in which RSC is compromised.