Inactivation of the striatum in aged rats rescues their ability to learn a hippocampus-sensitive spatial navigation task

Abstract

Studies of age-related changes in learning and memory often focus on hippocampus-sensitive tasks and reveal age-associated impairments across numerous species and contexts. However, cognitive decline with advanced age is not all-encompassing; for example, forms of striatum-sensitive learning are conserved or enhanced with age. Under certain conditions, hippocampal and striatal memory systems function in opposition. In young adult rodents, disruption of one structure can enhance learning on tasks dependent on the other, suggesting that competitive interactions across memory systems contribute to learning and memory abilities. This report examines whether imbalances across memory systems might contribute to cognitive aging. We inactivated the striatum using central infusions of lidocaine (sodium channel blocker) prior to hippocampus-sensitive spatial (place) training in young (3-4-month-old) and old (24-25-month-old) F344 male rats. Consistent with prior work, vehicle-infused old rats exhibited place learning impairments relative to young rats. Additionally, striatal inactivation enhanced learning in old rats, but not young rats, abolishing the age-related impairment. These findings suggest that age-related declines in learning tasks thought to engage the hippocampus may stem from exaggerated interference from other memory systems and that interventions to target the striatum may reverse some age-related learning decrements.

Keywords: Aging; Hippocampus; Lidocaine; Memory modulation; Memory system competition; Spatial learning; Striatum.

Figure 1.. Rescue of place learning in aged rats.

Learning was quantified as A) choice accuracy across five trial blocks (20 trials each) and B) the number of trials to reach 14 correct out of the 15 most recent trials. A) Although choice accuracy was at chance levels at the start of training, old control (aCSF) rats showed reduced trial accuracy overall compared to young rats. Pre-training lidocaine (Lido) infusions into striatum reversed this effect: Old lidocaine-treated rats showed greater choice accuracy than did old controls and comparable learning rates to those in young rats. B) Comparable effects were observed upon quantifying trials to criterion. Old controls took more trials than did young controls to reach the learning criterion. Lidocaine infusions into striatum reduced the number of trials to reach criterion in old rats, reversing the age-related decrement in learning. No infusion effects were observed in young rats. Data are shown as A) mean plus standard error of the mean and B) median with the interquartile range. Young aCSF, n = 8; young lidocaine, n = 5; old aCSF, n = 6; old lidocaine, n = 5. * p < 0.05.

Figure 2.. Sites of dorsolateral striatal infusions.

A) Representative cresyl violet-stained section showing site of infusion and relatively modest histological damage from cannula implantation. B) Cannula tips, shown here as dots, were mapped to a stereotaxic rat brain atlas (Swanson, 2004).