title: Caspase-3 deficiency results in disrupted synaptic homeostasis and impaired attention control.
abstract: The ability to attend to relevant stimuli and to adapt dynamically as demands change is a core aspect of cognition, and one that is impaired in several neuropsychiatric diseases, including attention deficit/hyperactivity disorder. However, the cellular and molecular mechanisms underlying such cognitive adaptability are poorly understood. We found that deletion of the caspase-3 gene, encoding an apoptosis protease with newly discovered roles in neural plasticity, disrupts attention in mice while preserving multiple learning and memory capabilities. Attention-related deficits include distractibility, impulsivity, behavioral rigidity, and reduced habituation to novel stimuli. Excess exploratory activity in Casp3(-/-) mice was correlated with enhanced novelty-induced activity in the dentate gyrus, which may be related to our findings that caspase-3 is required for homeostatic synaptic plasticity in vitro and homeostatic expression of AMPA receptors in vivo in response to chronic or repeated stimuli. These results suggest an important role for caspase-3 in synaptic suppression of irrelevant stimuli.
authors: Departments of Neuroscience, and shihchil@gene.com kimbersc@gene.com.
authors: Shih-Ching
authors: SC
authors: Lo
authors: Departments of Neuroscience, and.
authors: Yuanyuan
authors: Y
authors: Wang
authors: Departments of Neuroscience, and.
authors: Martin
authors: M
authors: Weber
authors: Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080.
authors: Jessica L
authors: http://orcid.org/0000-0003-2619-3579
authors: JL
authors: Larson
authors: Departments of Neuroscience, and shihchil@gene.com kimbersc@gene.com.
authors: Kimberly
authors: http://orcid.org/0000-0003-0568-802X
authors: K
authors: Scearce-Levie
authors: Departments of Neuroscience, and.
authors: Morgan
authors: M
authors: Sheng
mesh_terms: D000818:Animals; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology; D053148:Caspase 3 / Q000172:deficiency* / Q000235:genetics; D018891:Dentate Gyrus / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D006706:Homeostasis; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D013569:Synapses / Q000502:physiology*
chemical_list: D053148:Caspase 3
keywords: ADHD; LTD; attention control; caspase-3; homeostatic synaptic plasticity; novelty habituation
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