Neurexin alternative splicing, motor learning, and addiction

Neurexin 选择性剪接、运动学习和成瘾

• 批准号: 8450462
• 负责人: David Christopher Martinelli
• 金额: $ 5.39万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8450462
• 关键词: Alleles; Alternative Splicing; Autistic Disorder; Behavior; Biological Assay; Biological Models; Brain; Brain region; Chronic; Cocaine; Cocaine Abuse; Corpus striatum structure; Cues; Data; Disease; Dorsal; Drug Addiction; Drug usage; Enhancers; Enterobacteria phage P1 Cre recombinase; Exons; Functional disorder; Genes; Goals; Human; Human Genetics; Injection of therapeutic agent; Intervention; Knockout Mice; Learning; Link; Measures; Motor Skills; Mus; Mutant Strains Mice; Mutation; Neurons; Output; Parkinson Disease; Pathway interactions; Pharmaceutical Preparations; Play; Predisposition; Proteins; Research; Rewards; Role; Schizophrenia; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic Intervention; Ventral Striatum; Virus; Work; addiction; cognitive function; drug reward; experience; immunocytochemistry; inhibitor/antagonist; insight; motor learning; neuropsychiatry; novel; preference; research study; retinal rods

DESCRIPTION (provided by applicant): The striatum participates in many brain functions, in particular in our ability to learn and retain motor skills and in drug reward behaviors. Changes in striatal function are implicated in multiple neuropsychiatric diseases, including drug addiction. Importantly, human genetic studies have linked the neurexin genes to drug addiction predisposition. I present here preliminary data suggesting that neurexin mutant mice display alterations in striatum-dependent behaviors: an enhancement of motor learning and a reduction in cocaine reward, which suggest a mechanistic commonality between the two behaviors and suggest a model system to investigate the noted connection between the human neurexin genes and drug addiction predisposition. I propose experiments to test the hypothesis that alternative splicing at a single exon in the neurexin-3 gene modulates these striatum-dependent behaviors. I also propose to identify the specific brain regions that project to the striatum and are responsible for supplying the behavior-modifying neurexin protein. The goal of this research is to advance our understanding of the role of neurexin alternative splicing in cognitive function and to identify brain circuitry likely relevant to diseases with a striatal dysfunction component, such as drug addiction. Additionally, by defining the function of the neurexin genes in striatum-dependent behaviors, the proposed research will provide insight into the connection between mutations in human neurexin genes and drug addiction predisposition and point to a potential target for therapeutic intervention.

描述（由申请人提供）：纹状体参与许多大脑功能，特别是我们学习和保持运动技能的能力以及药物奖励行为。的变化