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The Journal of Neuroscience, October 5, 2005, 25(40):9112-9123; doi:10.1523/JNEUROSCI.1982-05.2005

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Behavioral/Systems/Cognitive
Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

Karin Schon,^1,2 Alireza Atri,^2,5 Michael E. Hasselmo,^1,2,3 Marisa D. Tricarico,² Matthew L. LoPresti,^2,3 and Chantal E. Stern^1,2,3,4

¹Department of Psychology, ²Center for Memory and Brain, and ³Program in Neuroscience, Boston University, Boston, Massachusetts 02215, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, and ⁵Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Recent computational modeling and slice physiology studies have suggested that long-term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine.

Key words: memory formation; cholinergic; fMRI; medial temporal lobe; delayed match to sample; computational modeling

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Received May 17, 2005; revised August 9, 2005; accepted August 20, 2005.

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