Caspase-3 deficiency results in disrupted synaptic homeostasis and impaired attention control.
J Neurosci
; 35(5): 2118-32, 2015 Feb 04.
Article
in En
| MEDLINE
| ID: mdl-25653368
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Attention
/
Attention Deficit Disorder with Hyperactivity
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Synapses
/
Caspase 3
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Homeostasis
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2015
Document type:
Article