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The Journal of Neuroscience, February 20, 2008, 28(8):1841-1853; doi:10.1523/JNEUROSCI.4629-07.2008

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Behavioral/Systems/Cognitive
Activation of the Medial Septum Reverses Age-Related Hippocampal Encoding Deficits: A Place Field Analysis

Simona Sava^1,2 and Etan J. Markus¹

¹Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, Connecticut 06269, and ²Department of Psychiatry, Harvard Medical School and Brain Imaging Center, McLean Hospital, Belmont, Massachusetts 02478

Correspondence should be addressed to Dr. Etan J. Markus, Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, U-1020, Storrs, CT 06269. Email: etan.markus{at}uconn.edu

When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. The medial septum is hypothesized to modulate whether the hippocampus engages in retrieval or encoding. The cholinergic agonist carbachol was infused into the medial septum, and hippocampal CA1 place cells were recorded in freely moving rats. In a familiar environment, septal activation impaired the retrieval of a previously stored hippocampal place cell representation regardless of age. When the environment was changed, medial septal activation impaired the encoding process in young, but facilitated the encoding of the new information in aged rats. Moreover, the improved encoding was evident during a subsequent exposure to the modified environment 24 h later. The findings support the role the septum plays in modulating hippocampal retrieval/encoding states. Furthermore, our data indicate a mechanism of age-related cognitive impairment.

Key words: aging; cholinergic; carbachol; memory; remapping; place field

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Received June 8, 2007; revised Dec. 12, 2007; accepted Dec. 31, 2007.

Correspondence should be addressed to Dr. Etan J. Markus, Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, U-1020, Storrs, CT 06269. Email: etan.markus{at}uconn.edu

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