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: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506059
• 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.

树突对应于神经元的接收装置，随着时间的推移整合绝大多数突触输入。枝晶表现出活性离子电导的大的多样性，并且因此作为非线性信号装置操作。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作用范围，并且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。最近的方法的进步，包括能够监测光学局部钙离子浓度升高的树突隔室使用双光子显微镜在脑切片和体内，使近距离观察的过程中发生的树突和的方式，通过该信息从突触转化为神经代码和修改的活动在树突发育和可塑性的变化。尽管如此，不同类型细胞树突中活跃树突过程的机制和作用仍然未被探索。局部回路GABA能中间神经元控制许多脑区的信息整合和传递。尽管不同类型的中间神经元表现出高度复杂的树突组织，具有大量的电压门控离子电导和特定的神经递质受体，但中间神经元树突很少受到关注。我们建议探索活性依赖性招聘和功能意义的活性树突电导在兴奋性突触的抑制性中间神经元使用相结合的靶向体细胞膜片钳和尖锐的细胞内记录，双光子显微镜（Ca2+成像和uncaging），光遗传学，荧光，和神经解剖学在脑切片和体内。由于树突状细胞信号处理的功能组织是学习，记忆和更高的认知功能在多种神经和精神健康疾病的影响的基础，这项研究将是有价值的细胞生物学家和神经科学家在细胞和系统神经科学和认知障碍领域的工作。