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Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II
C Chen1, D G Rainnie, R W Greene
1Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA.
Abstract:
Mice deficient for the gene encoding alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.
Insights
Alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII) knockout mice exhibit altered fear and aggression. These mice offer a model for studying the molecular basis of emotional disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Genetics
Background:
- Alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII) is crucial for synaptic plasticity and learning.
- Understanding the role of alpha-CaMKII in behavior is essential for neurological research.
Purpose of the Study:
- To investigate the behavioral and cellular consequences of alpha-CaMKII deficiency in mice.
- To establish alpha-CaMKII knockout mice as a model for emotional disorders.
Main Methods:
- Generation of alpha-CaMKII heterozygous and homozygous knockout mice.
- Behavioral testing including fear response and aggression paradigms.
- Electrophysiological recordings (extracellular and whole-cell patch clamp) of serotonergic neurons in the dorsal raphe nucleus.
Main Results:
- Heterozygous mice showed decreased fear response and increased defensive aggression without cognitive deficits.
- Homozygous mice displayed abnormal behavior across all tested paradigms.
- Reduced serotonin release was observed in dorsal raphe serotonergic neurons of knockout mice.
Conclusions:
- Alpha-CaMKII knockout mice, particularly heterozygotes, serve as a valuable model for studying the molecular and cellular underpinnings of fear and aggression.
- These findings link a specific molecular deficit (alpha-CaMKII deficiency) to complex emotional behaviors and neurotransmitter dysfunction.