Abstract
Little is known about the molecular mechanisms of learned and innate fear. We have identified stathmin, an inhibitor of microtubule formation, as highly expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical structures that send information to the LA about the conditioned (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP). The knockout mice also exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments. By contrast, these mice do not show deficits in the water maze, a spatial task dependent on the hippocampus, where stathmin is not normally expressed. We therefore conclude that stathmin is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amygdala / metabolism
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Amygdala / physiology*
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Animals
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Animals, Newborn
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Behavior, Animal / physiology
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Cerebral Cortex / metabolism
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Cerebral Cortex / physiology
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Conditioning, Psychological / physiology*
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Electrophysiology
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Fear / physiology*
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Gene Expression / genetics
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Gene Expression Regulation, Developmental / genetics
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Hippocampus / physiology
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Immunohistochemistry
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In Situ Hybridization
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In Vitro Techniques
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Long-Term Potentiation / physiology
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Maze Learning / physiology
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Memory Disorders / genetics
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Memory Disorders / physiopathology
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Mice
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Mice, Knockout
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Microtubules / metabolism
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Neural Pathways / physiology
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Neurons / metabolism
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Receptors, GABA-A / physiology
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Receptors, N-Methyl-D-Aspartate / physiology
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Stathmin / genetics
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Stathmin / physiology*
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Synaptic Transmission / physiology
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Thalamus / metabolism
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Thalamus / physiology
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Time Factors
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Tubulin / analysis
Substances
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Receptors, GABA-A
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Receptors, N-Methyl-D-Aspartate
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Stathmin
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Tubulin