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albert einstein Music For Study, Focus, Memory, relax, stimulate the brain and smart part -1Abstract Memory deficits are one of the disabling impairments associated with autism, mental retardation, and schizophrenia.
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Because the underlying genetic and neuronal mechanisms of memory impairments are still poorly understood, mechanism-based therapeutic options do not exist to ameliorate such impairment, hindering the effective integration of patients into society. Interestingly, a high activity allele of catechol-O-methyl-transferase COMT is associated with lower levels of working memory performance after, but not before, puberty in children and adolescents.
Our Einstein Working Memory mouse work shows that elevated activity of human COMT impairs working memory of mice at 2 months but not 1 month of age, where 1 month of age corresponds to puberty in the mouse. While this correlation in humans and mice suggests that there is a developmental timetable along which COMT levels begin to exert an influence on working memory, these studies did not elevate COMT levels at specific brain loci and developmental time points.
The precise anatomical and cellular substrates and their developmental programming through which high COMT activity affects working memory capacity are still poorly understood. The objective of the proposed project is to test the overarching hypothesis that working memory and associated synaptic plasticity become increasingly dependent Einstfin an endogenous dopamine tone in the medial prefrontal cortex or hippocampus during postnatal development.
To test this hypothesis, the PI has developed a lentiviral vector that temporally and spatially up-regulates COMT in the mouse brain. A team of investigators will achieve the following Specific Aims: Specific Aim 1 : To ascertain the impact of elevated COMT expression in the medial prefrontal cortex or hippocampus on working memory capacity at specific developmental time points. Specific Aim 2 : To determine the impact of spatially and temporally targeted Einstein Working Memory in an endogenous dopamine tone Worrking synaptic plasticity in the prefrontal cortex and hippocampus.
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Upon completion of the proposed Einstein Working Memory, these technically innovative experiments will, for the first time, identify the anatomical and cellular mechanisms through which an endogenous dopamine tone determines the developmental maturation of working memory capacity and synaptic plasticity.
Identifying the developmental time window, anatomical region sand cellular substrate s necessary for an endogenous dopamine tone to induce behavioral and cellular working memory phenotypes will have a major impact on our understanding of working memory. Because working memory deficits have been observed in individuals with mental retardation, autism, and schizophrenia, this proposal could lead to a Worrking understanding of the neurobiological substrates for one Einstein Working Memory of developmental neuropsychiatric disorders.
Public Health Relevance Cognitive impairments are a major obstacle to integration into society for individuals with autism spectrum disorders, schizophrenia and mental retardation. The proposed studies will test the innovative concept that heightened COMT activity affects the developmental maturation of working memory capacity and synaptic plasticity. The outcome of the proposed Mwmory will provide a solid foundation to more fully understand the mechanisms for developmental memory impairments seen in the neuropsychiatric disorders.]
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