Evidence for a virtual human analog of a rodent relational memory task: A study of aging and fMRI in young adults
Hippocampus. 2011-06-08; 22(4): 869-880
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1. Hippocampus. 2012 Apr;22(4):869-80. doi: 10.1002/hipo.20948. Epub 2011 Jun 8.
Evidence for a virtual human analog of a rodent relational memory task: a study
of aging and fMRI in young adults.
Etchamendy N(1), Konishi K, Pike GB, Marighetto A, Bohbot VD.
(1)Department of Psychiatry, Douglas Mental Health University Institute, McGill
University, Verdun, Quebec, Canada H4H 1R3.
A radial maze concurrent spatial discrimination learning paradigm consisting of
two stages was previously designed to assess the flexibility property of
relational memory in mice, as a model of human declarative memory. Aged mice and
young adult mice with damage to the hippocampus, learned accurately Stage 1 of
the task which required them to learn a constant reward location in a specific
set of arms (i.e., learning phase). In contrast, they were impaired relative to
healthy young adult mice in a second stage when faced with rearrangements of the
same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is
thought to derive from insufficient relational processing by the hippocampus
during initial learning (Stage 1) which favors stimulus-response learning, a form
of procedural learning. This was proposed as a model of the selective declarative
and relational memory decline classically described in elderly people. As a first
step to examine the validity of this model, we adapted this protocol to humans
using a virtual radial-maze. (1) We showed that performance in the flexibility
probes in young and older adults positively correlated with performance in a
wayfinding task, suggesting that our paradigm assesses relational memory. (2) We
demonstrated that older healthy participants displayed a deficit in the
performance of the flexibility probes (Stage 2), similar to the one previously
seen in aged mice. This was associated with a decline in the wayfinding task. (3)
Our fMRI data in young adults confirmed that hippocampal activation during early
discrimination learning in Stage 1 correlated with memory flexibility in Stage 2,
whereas caudate nucleus activation in Stage 1 negatively correlated with
subsequent flexibility. By enabling relational memory assessment in mice and
humans, our radial-maze paradigm provides a valuable tool for translational
Copyright © 2011 Wiley Periodicals, Inc.
PMID: 21656872 [Indexed for MEDLINE]