Caspase-3 deficiency results in disrupted synaptic homeostasis and impaired attention control.
Shih-Ching LoYuanyuan WangMartin WeberJessica L LarsonKimberly A Scearce-LevieMorgan ShengPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2015)
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.
Keyphrases
- cell death
- attention deficit hyperactivity disorder
- working memory
- induced apoptosis
- endoplasmic reticulum stress
- cell cycle arrest
- autism spectrum disorder
- oxidative stress
- poor prognosis
- high fat diet induced
- drug induced
- traumatic brain injury
- genome wide
- signaling pathway
- type diabetes
- high glucose
- gene expression
- mild cognitive impairment
- obsessive compulsive disorder
- metabolic syndrome
- dna methylation
- copy number
- insulin resistance
- prefrontal cortex
- single molecule
- endothelial cells
- long non coding rna
- transcription factor
- skeletal muscle
- replacement therapy
- functional connectivity