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CA3 NMDA receptors are required for experience-dependent shifts in hippocampal activity.

Authors
  • Kent, Kelly1
  • Hess, Kenneth
  • Tonegawa, Susumu
  • Small, Scott A
  • 1 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Type
Published Article
Journal
Hippocampus
Publication Date
Jan 01, 2007
Volume
17
Issue
10
Pages
1003–1011
Identifiers
PMID: 17607765
Source
Medline
License
Unknown

Abstract

The anatomical distribution of sensory-evoked activity recorded from the hippocampal long-axis can shift depending on prior experience. In accordance with Marr's computational model of hippocampal function, CA3 NMDA receptors have been hypothesized to mediate this experience-dependent shift in hippocampal activity. Here we tested this hypothesis by investigating genetically-modified mice in which CA3 NMDA receptors are selectively knocked-out (CA3-NR1 KO). First, we were required to develop an fMRI protocol that can record sensory-evoked activity from the mouse hippocampal long-axis. This goal was achieved in part by using a dedicated mouse scanner to image odor-evoked activity, and by using non-EPI (echo planer imaging) pulse sequences. As in humans, odors were found to evoke a ventral-predominant activation pattern in the mouse hippocampus. More importantly, odor-evoked activity shifted in an experience-dependent manner. Finally, we found that the experience-dependent shift in hippocampal long-axis activity is blocked in CA3-NR1 knock-out mice. These findings establish a cellular mechanism for the plasticity imaged in the hippocampal long-axis, suggesting how experience-dependent modifications of hippocampal activity can contribute to its mnemonic function.

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