Impaired spatial memory performance in a rat model of neuropathic pain is associated with reduced hippocampus-prefrontal cortex connectivity

• Published in: The Journal of neuroscience Vol. 33; no. 6; pp. 2465 - 2480
• Main Authors: Cardoso-Cruz, Helder, Lima, Deolinda, Galhardo, Vasco
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 06-02-2013
• Subjects: Animals; Disease Models, Animal; Hippocampus - physiopathology; Male; Maze Learning - physiology; Memory Disorders - physiopathology; Neural Inhibition - physiology; Neural Pathways - physiology; Neuralgia - physiopathology; Pain Measurement - methods; Prefrontal Cortex - physiopathology; Rats; Rats, Sprague-Dawley; Spatial Behavior - physiology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.5197-12.2013

Chronic pain patients commonly complain of working memory deficits, but the mechanisms and brain areas underlying this cognitive impairment remain elusive. The neuronal populations of the mPFC and dorsal CA1 (dCA1) are well known to form an interconnected neural circuit that is crucial for correct performance in spatial memory-dependent tasks. In this study, we investigated whether the functional connectivity between these two areas is affected by the onset of an animal model of peripheral neuropathic pain. To address this issue, we implanted two multichannel arrays of electrodes in the mPFC and dCA1 of rats and recorded the neuronal activity during a food-reinforced spatial working memory task in a reward-based alternate trajectory maze. Recordings were performed for 3 weeks, before and after the establishment of the spared nerve injury model of neuropathy. Our results show that the nerve lesion caused an impairment of working memory performance that is temporally associated with changes in the mPFC populational firing activity patterns when the animals navigated between decision points-when memory retention was most needed. Moreover, the activity of both recorded neuronal populations after the nerve injury increased their phase locking with respect to hippocampal theta rhythm. Finally, our data revealed that chronic pain reduces the overall amount of information flowing in the fronto-hippocampal circuit and induces the emergence of different oscillation patterns that are well correlated with the correct/incorrect performance of the animal on a trial-by-trial basis. The present results demonstrate that functional disturbances in the fronto-hippocampal connectivity are a relevant cause for pain-related working memory deficits.