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The Journal of Neuroscience, May 7, 2008, 28(19):4974-4981; doi:10.1523/JNEUROSCI.5622-07.2008

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Behavioral/Systems/Cognitive
Functional Magnetic Resonance Imaging of Delay and Trace Eyeblink Conditioning in the Primary Visual Cortex of the Rabbit

Michael J. Miller,^1,2 Craig Weiss,⁴ Xiaomu Song,^2,3 Gheorghe Iordanescu,^2,3 John F. Disterhoft,⁴ and Alice M. Wyrwicz^2,3

¹Biomedical Engineering Department, Northwestern University, Evanston, Illinois 60201, ²Center for Basic Magnetic Resonance Research, Evanston Northwest Healthcare Research Institute, Evanston, Illinois 60201, and ³Departments of Radiology and ⁴Physiology, Feinberg Medical School, Northwestern University, Chicago, Illinois 60611

Correspondence should be addressed to Alice M. Wyrwicz, Center for Basic Magnetic Resonance Research, Evanston Northwest Healthcare Research Institute, 1033 University Place, Suite 100, Evanston, IL 60201. Email: a-wyrwicz{at}northwestern.edu

The primary sensory cortices have been shown in recent years to undergo experience- and learning-related plasticity under a variety of experimental circumstances. In this study, we used functional magnetic resonance imaging (fMRI) in parallel with both delay and trace eyeblink conditioning to image the learning-related functional activation within the primary visual cortex (V1) of awake, behaving rabbits. We expected that the differing level of forebrain dependence between these two conditioning paradigms should produce a differential blood oxygenation level-dependent (BOLD) functional response in V1. Our results showed a significant expansion of activated volume within V1, particularly early in learning, after training with the more cognitively demanding trace paradigm. In contrast, the simpler delay paradigm produced an increase in the magnitude of the BOLD response in activated voxels, but no significant change in activated volume. No accompanying learning-related changes were observed in the primary somatosensory cortex, which mediates the unconditioned stimulus. These results suggest that the recruitment of additional neurons within V1 is necessary to support the more demanding memory imposed by the trace interval. To our knowledge, this work is the first functional imaging study to compare directly trace and delay eyeblink conditioning in an animal model.

Key words: fMRI; eyeblink conditioning; visual cortex; rabbit; learning; memory

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Received Dec. 19, 2007; revised March 4, 2008; accepted March 28, 2008.

Correspondence should be addressed to Alice M. Wyrwicz, Center for Basic Magnetic Resonance Research, Evanston Northwest Healthcare Research Institute, 1033 University Place, Suite 100, Evanston, IL 60201. Email: a-wyrwicz{at}northwestern.edu

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