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The Journal of Neuroscience, August 20, 2008, 28(34):8387-8396; doi:10.1523/JNEUROSCI.1924-08.2008

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Behavioral/Systems/Cognitive
Dissociable Roles for Cortical and Subcortical Structures in Memory Retrieval and Acquisition

Anna S. Mitchell, Philip G. F. Browning, Charles R. E. Wilson, Mark G. Baxter, and David Gaffan

Department of Experimental Psychology, Oxford University, Oxford OX1 3UD, United Kingdom

Correspondence should be addressed to Dr. Anna S. Mitchell, Department of Experimental Psychology, Oxford University, South Parks Road, Oxford OX1 3UD, UK. Email: anna.mitchell{at}psy.ox.ac.uk

The relationship between anterograde and retrograde amnesia remains unclear. Previous data from both clinical neuropsychology and monkey lesion studies suggest that damage to discrete subcortical structures leads to a relatively greater degree of anterograde than retrograde amnesia, whereas damage to discrete regions of cortex leads to the opposite pattern of impairments. Nevertheless, damage to the medial diencephalon in humans is associated with both retrograde and anterograde amnesia. In the present study, we sought to reconcile this by assessing retention as well as subsequent relearning and new postoperative learning. Rhesus monkeys learned 300 unique scene discriminations preoperatively, and retention was assessed in a preoperative and postoperative one-trial retrieval test. Combined bilateral subcortical lesions to the magnocellular mediodorsal thalamus and fornix impaired postoperative retention of the preoperatively acquired information. In addition, subsequent relearning and new postoperative learning were also impaired. This contrasts with the effects of a discrete lesion to just one of these structures, after which retention is intact in both cases. Discrete bilateral ablations to the entorhinal cortex impaired retention but had no effect on new learning. Combined with previous work from our laboratory, these results support the hypothesis that subcortical damage has a relatively greater effect on new learning, and cortical damage has a relatively greater effect on retention. Furthermore, the results demonstrate that retrograde amnesia occurs as a result of subcortical damage only if it is widespread, leading to an extensive disruption of cortical functioning. Damage of this nature may account for dense amnesia.

Key words: mediodorsal thalamus; fornix; entorhinal cortex; amnesia; acquisition; retrieval

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Received March 14, 2008; revised June 11, 2008; accepted June 23, 2008.

Correspondence should be addressed to Dr. Anna S. Mitchell, Department of Experimental Psychology, Oxford University, South Parks Road, Oxford OX1 3UD, UK. Email: anna.mitchell{at}psy.ox.ac.uk

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