The function of the working memory circuits following irradiation to the growing brain

Progressive cognitive decline is a chronic side effect of radiotherapy in brain cancer patients, which is especially severe in those treated during childhood. Major cognitive disabilities after cranial radiation arise from damage in Prefrontal cortex (PFC) and the Hippocampus, whose connectivity is critical for different memory demands. To investigate how early-age irradiation affects memory in the adulthood, we submitted rat pups to cranial radiation at an age resembling toddler age in humans. After 2 months, rats were tested on a Novel Object Recognition (NOR) task and Object Location Recognition (OLR) task. Despite not significant effects were observed in the NOR task, the OLR task was more sensitive to see differences between irradiated and sham controls, suggesting that cranial radiation does not impair recognition memory for objects per se but for object-place associations. To investigate the functional shortcomings in the irradiated brain, we used large-scale electrophysiological recordings is animals solving a Delayed non-match-to-sample task. Although a similar oscillatory activity was found in both irradiated and control animals, cranial radiation induced a lower functional connectivity in the PFC-Hippocampus circuit under high working-memory demands, which correlated with a lower behavioural performance in the task. In this way, we described herein that the cognitive decline often observed in cancer survivors is related in part to a lower functional connectivity between structures related memory and executive function.