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The Journal of Neuroscience, December 20, 2006, 26(51):13143-13155; doi:10.1523/JNEUROSCI.3803-06.2006

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Behavioral/Systems/Cognitive
Apparent Encoding of Sequential Context in Rat Medial Prefrontal Cortex Is Accounted for by Behavioral Variability

David R. Euston and Bruce L. McNaughton

Arizona Research Laboratories Division of Neural Systems, Memory, and Aging, University of Arizona, Tucson, Arizona 85724-5115

Correspondence should be addressed to Bruce L. McNaughton, Arizona Research Laboratory Division of Neural Systems, Memory, and Aging, Life Sciences North Building, Room 384, University of Arizona, Tucson, AZ 85724-5115. Email: bruce{at}nsma.arizona.edu

Simple sequences can be represented via asymmetrically linked neural assemblies, provided that the elements of the sequence are unique. When elements repeat, however (e.g., A-B-C-B-A), the same element belongs to two separate "sequential contexts," and a more complex encoding mechanism is required. To enable correct sequence performance, some neural structure must provide a disambiguating signal that differentiates the two sequential contexts (i.e., B as an element of "A-B" as opposed to "C-B"). The disambiguating signal may derive from a form of working memory, or, in some cases, a simple timing mechanism may suffice. To investigate the possible role of medial prefrontal cortex in complex sequence encoding, rats were trained on a spatial sequence containing two adjacent repeated segments (e.g., A-B-C-D-B-C-E). The double-repeat procedure minimized behavioral differences in the second leg (C) of the repeat subsequence that arise in the first leg (B) because of differences in the entry point (e.g., A-B vs D-B). Far more cells were context sensitive along the first leg than along the second (36 vs 9%), and most of the differences were accounted for by systematic variations in the rat's trajectory, which were much larger along the first leg. There is thus little evidence for sequential context-discriminative activity in the medial prefrontal cortex that cannot plausibly be accounted for by context-dependent behavior. The finding that the rodent medial prefrontal cortex is highly sensitive to sensory–behavioral variables raises doubts about previous experiments that purport to show working memory-related activity in this region.

Key words: delayed alternation; prefrontal; prelimbic cortex; rat; sequence disambiguation; working memory


Received May 3, 2006; revised Nov. 3, 2006; accepted Nov. 4, 2006.

Correspondence should be addressed to Bruce L. McNaughton, Arizona Research Laboratory Division of Neural Systems, Memory, and Aging, Life Sciences North Building, Room 384, University of Arizona, Tucson, AZ 85724-5115. Email: bruce{at}nsma.arizona.edu




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