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

Neurobiol Learn Mem. 2020 Jul:172:107231. doi: 10.1016/j.nlm.2020.107231. Epub 2020 Apr 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Cognitive Aging / physiology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Hippocampus / physiology*
  • Lidocaine / administration & dosage
  • Male
  • Rats, Inbred F344
  • Spatial Navigation / drug effects
  • Spatial Navigation / physiology*
  • Voltage-Gated Sodium Channel Blockers / administration & dosage

Substances

  • Voltage-Gated Sodium Channel Blockers
  • Lidocaine