Evidence for a virtual human analog of a rodent relational memory task: A study of aging and fMRI in young adults

Nicole Etchamendy, Kyoko Konishi, G. Bruce Pike, Aline Marighetto, Véronique D. Bohbot
Hippocampus. 2011-06-08; 22(4): 869-880
DOI: 10.1002/hipo.20948

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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.

Author information:
(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
research.

Copyright © 2011 Wiley Periodicals, Inc.

DOI: 10.1002/hipo.20948
PMID: 21656872 [Indexed for MEDLINE]


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