Dendritic signal processing and functional compartmentalization in GABAergic interneurons

GABA能中间神经元的树突信号处理和功能划分

• 批准号: 342292-2012
• 负责人: Topolnik, LisaYelyzaveta
• 金额: $ 2.48万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629596
• 关键词: Dendritic; signal; processing; functional; compartmentalization

Dendrites correspond to a receiving apparatus of the neuron, integrating the vast majority of synaptic inputs over time. Dendrites exhibit a large diversity of active ion conductances and, therefore, operate as non-linear signaling devices. Calcium signal represents an important aspect of dendritic integration. It may have different spatial and temporal ranges of action, and can exert various functions from induction of synaptic plasticity to local tuning of neuronal firing. Recent methodological advances, including the ability to monitor optically local Ca2+ elevations in dendritic compartments using two-photon microscopy in brain slices and in vivo, have enabled the close observation of the processes that occur within dendrites and of the manner via which information received from synapses is transformed into a neural code and modified by changes in activity during dendritic development and plasticity. Nonetheless, the mechanisms and roles of active dendritic processes in dendrites of different cell types remain unexplored. Local circuit GABAergic interneurons control the integration and transfer of information in many brain regions. Despite the fact that different types of interneurons exhibit a highly complex dendritic organization, with a large variety of voltage-gated ion conductances and specific neurotransmitter receptors, interneuron dendrites have received little attention. We propose to explore the activity-dependent recruitment and the functional significance of active dendritic conductances at excitatory synapses of inhibitory interneurons using a combination of targeted somatic patch-clamp and sharp intracellular recordings, two-photon microscopy (Ca2+ imaging and uncaging), optogenetics, immunohistoshemistry, and neuroanatomy in brain slices and in vivo. As the functional organization of dendritic signal processing is fundamental for the learning, memory and higher cognitive functions affected in multiple neurological and mental health disorders, this study will be of value to cell biologists and neuroscientists working in the fields of cellular and system neuroscience and cognitive disorders.

树突与神经元的接收装置相对应，随着时间的推移，树突整合了绝大多数的突触输入。树突表现出活性离子电导率的多样性，因此，作为非线性信号器件运行。钙信号是树突整合的一个重要方面。它可能具有不同的空间和时间范围的作用，并可以发挥从诱导突触可塑性到局部调节神经元放电的各种功能。最近的方法学进展，包括在脑切片和体内使用双光子显微镜监测树突腔室光学局部Ca2+升高的能力，已经能够近距离观察树突内发生的过程，以及从突触接收的信息转化为神经密码的方式，并通过树突发育和可塑性期间活动的变化进行修改。然而，在不同细胞类型的树突中，活性树突过程的机制和作用仍未被探索。局部回路gaba能中间神经元控制着大脑许多区域的信息整合和传递。尽管不同类型的中间神经元表现出高度复杂的树突组织，具有各种各样的电压门控离子电导和特定的神经递质受体，但中间神经元树突却很少受到关注。我们建议利用靶向体细胞膜片钳和细胞内尖锐记录、双光子显微镜（Ca2+成像和解封）、光遗传学、免疫组织化学和脑切片和体内神经解剖学的结合，探索抑制性中间神经元兴奋性突触活跃树突电导的活动依赖性募集和功能意义。由于树突信号处理的功能组织是多种神经和精神健康障碍影响学习、记忆和高级认知功能的基础，因此本研究将对细胞生物学家和从事细胞和系统神经科学以及认知障碍领域的神经科学家具有重要价值。