Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning

The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information as follows: entorhinal cortex [rightward arrow] dentate gyrus [rightward arrow] CA3 [rightward arrow] CA1 [rightward arr...

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Published in:Science (American Association for the Advancement of Science) 2008-02, Vol.319 (5867), p.1260-1264
Main Authors: Nakashiba, Toshiaki, Young, Jennie Z, McHugh, Thomas J, Buhl, Derek L, Tonegawa, Susumu
Format: Article
Language:English
Subjects:
Action Potentials
Anatomical correlates of behavior
Animal cognition
Animal memory
Animals
Behavioral psychophysiology
Biological and medical sciences
Brain
Brain research
Chlorofluorocarbons
Crosses, Genetic
Dentate Gyrus - physiology
Electrophysiology
Entorhinal Cortex - physiology
Excitatory Postsynaptic Potentials
Female
Freezing
Fundamental and applied biological sciences. Psychology
Genotypes
Hippocampus
Hippocampus - physiology
Interneurons - physiology
Male
Maze Learning
Memory
Mental Recall
Metalloendopeptidases - genetics
Mice
Mice, Transgenic
Neural Pathways
Neurons
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Pyramidal cells
Pyramidal Cells - physiology
Rodents
Synapses
Synaptic Transmission
Tetanus Toxin - genetics
Transgenic animals
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Summary:The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information as follows: entorhinal cortex [rightward arrow] dentate gyrus [rightward arrow] CA3 [rightward arrow] CA1 [rightward arrow] entorhinal cortex) and the monosynaptic pathway (entorhinal cortex [rightward arrow] CA1 [rightward arrow] entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid one-trial contextual learning, for pattern completion-based memory recall, and for spatial tuning of CA1 cells.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1151120