4.7 Article

Caspase-3 Deficiency Results in Disrupted Synaptic Homeostasis and Impaired Attention Control

期刊

JOURNAL OF NEUROSCIENCE
卷 35, 期 5, 页码 2118-2132

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SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3280-14.2015

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ADHD; attention control; caspase-3; homeostatic synaptic plasticity; LTD; novelty habituation

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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.

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