The Role of Layer I Interneurons in the Activity-Dependent Assembly of the Somatosensory Cortex

第一层中间神经元在体感皮层活动依赖性组装中的作用

基本信息

批准号：
10425441
负责人：
Andrew Ferdynand Iannone
金额：
$ 5.18万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10425441
关键词：
Ablation Address Adult Affect Anatomy Animal Model Area Automobile Driving Behavior Behavior assessment Behavioral Characteristics Child Communities Dependence Development Developmental Process Discrimination Disease Electrophysiology (science)Electroporation Environmental Risk Factor Exhibits Eye Fiber Foundations Functional disorder Future Genes Genetic Genetic Diseases Genetic Risk Genetic Transcription Goals Impairment Incidence Interneurons Investigation Ligands Link Literature Maps Mediating Mentorship Molecular Molecular Target Morphology Mus N-Methyl-D-Aspartate Receptors Neonatal Neurons Neurosciences Pathogenesis Pattern Play Population Property Psychiatry Research Role Sensory Sensory Deprivation Somatosensory Cortex Stereotyping Symptoms Tactile Testing Texture Thalamic structure Vibrissae Viral Work autism spectrum disorder autistic axon growth barrel cortex cell type chemokine critical period experience gamma-Aminobutyric Acid high risk in utero individuals with autism spectrum disorder inhibitory neuron neuropsychiatry novel diagnostics novel therapeutics optogenetics postnatal programs recruit selective expression sensory cortex sensory input social deficits somatosensory symptomatology targeted treatment trait transcriptome sequencing

项目摘要

PROJECT SUMMARY/ABSTRACT Individuals with Autism Spectrum Disorders (ASD) and related neurodevelopmental diseases exhibit diverse manifestations of the stereotyped socioemotional limitations of these conditions. Prominently, deficits in the processing and interpreting of sensory inputs are consistently observed. Foundational studies implicate inhibitory interneuron dysfunction in the pathogenesis of ASD as well as the role of select interneuron subtypes in coordinating organization of sensory processing cortical areas. We hypothesize that sensory input to defined subtypes of inhibitory interneurons at early developmental stages is necessary to recruit genetic programs mediating the emergence of correctly patterned sensory maps. To test this hypothesis, we will demonstrate the local circuitry of a molecularly-defined subtype of superficial interneurons, which underlies their coordinating role in sensory cortical assembly, using a combination of immunohistochemical and electrophysiologic profiling. We will show that sensory deprivation though genetic ablation of a high-risk ASD gene in these interneurons alters their transcriptional programs in an activity- dependent manner. Finally, we will implicate the sensory-sensitive expression of an emerging subtype-defining gene in these interneurons as necessary and sufficient for driving their role in sharpening sensory maps at neonatal stages and for consequent tactile sensing behavior in adulthood. This proposal, undertaken with the intellectual support of the Tri-Institutional research community and the guidance of a mentorship team at the nexus of neuroscience and psychiatry, will address a significant gap in understanding the intersection between genetic risk and aberrant activity-dependent sensory processing circuitry in the emergence of ASD symptomatology.

项目摘要/摘要自闭症谱系障碍（ASD）和相关神经发育疾病的人表现出这些条件刻板印象的社会情感局限性的各种表现。突出地，感觉输入的处理和解释的缺陷始终是观察到。基础研究涉及抑制性间神经元功能障碍在发病机理中 ASD的以及精选中间亚型在协调感官组织中的作用处理皮质区域。我们假设对抑制性定义亚型的感觉输入早期发育阶段的中间神经元对于招募介导的遗传计划是必要的正确图案的感觉图的出现。为了检验这一假设，我们将证明浅表中间神经元的分子定义亚型的局部电路，这是其在感觉皮质组装中的协调作用的基础免疫组织化学和电生理分析。我们将证明这种感觉剥夺尽管这些中间神经元中高风险ASD基因的遗传消融改变了它们的转录以活动依赖的方式进行程序。最后，我们将暗示感官敏感的必要时在这些中间神经元中表达新兴亚型定义基因足以推动在新生儿阶段锐化的感觉图中的作用因此，成年后的触觉传感行为。这项提议与知识分子一起进行支持三机构研究社区和指导团队的指导神经科学和精神病学的联系将解决理解的重大差距遗传风险与异常活动依赖性感觉处理电路之间的交集 ASD症状学的出现。