CA3 NMDA receptors are required for experience-dependent shifts in hippocampal activity.
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.
Kent
Kelly
K
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.
Hess
Kenneth
K
Tonegawa
Susumu
S
Small
Scott A
SA
D000818:Animals; D001522:Behavior, Animal; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D009812:Odorants; D010100:Oxygen / Q000097:blood; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000378:metabolism*
C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010100:Oxygen