Local Circuits in the Olfactory Bulb

嗅球中的局部电路

• 批准号: 7467256
• 负责人: Ben W Strowbridge
• 金额: $ 28.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7467256
• 关键词: 4-Aminopyridine; AMPA Receptors; Accounting; Action Potentials; Address; Affect; Area; Attention; Behavioral; Biological Assay; Brain; Brain region; Cell physiology; Cells; Cholinergic Agents; Cholinergic Receptors; Chromosome Pairing; Class; Clinical; Complex; Computer information processing; Condition; Deep Brain Stimulation; Dendrites; Dendrodendritic Synapse; Electric Stimulation; Epilepsy; Exhibits; Fire - disasters; Frequencies; Goals; Golgi Apparatus; Hybrids; Image; Individual; Interneurons; Intervention; Kinetics; Lateral; Lead; Mediating; Muscarinics; N-Methyl-D-Aspartate Receptors; Neuraxis; Neurons; Neurosciences; Olfactory Receptor Neurons; Outcome; Output; Parkinson Disease; Pathway interactions; Pattern; Physiological; Play; Population; Property; Publishing; Range; Receptor Activation; Recurrence; Resistance; Role; Sensory; Sensory Process; Series; Signal Transduction; Site; Smell Perception; Source; Stimulus; Structure; Symptoms; Synapses; Synaptic Potentials; System; Techniques; Testing; Thalamic structure; Therapeutic; Training; Vertebral column; Work; afterpotential; basal forebrain; base; cell type; cholinergic; extracellular; granule cell; in vivo; nervous system disorder; novel therapeutics; olfactory bulb; postsynaptic; receptor; relating to nervous system; research study; response; tool

DESCRIPTION (provided by applicant): At the most elemental level, the central nervous system is involved in processing information represented by temporal patterns of action potentials in individual nerve cells. The olfactory system is an ideal brain region in which to study how sensory information is encoded. While olfactory transduction occurs in specialized olfactory receptor neurons, the actual work of generating temporally-modulated odorant-specific neural discharges begins in the olfactory bulb. Here the simple monotonic input from receptor neurons activates spatially-defined subpopulations of output neurons (mitral cells). However, mitral cells do not simply relay sensory information on to third-order brain areas. Instead, receptor neuron input interacts with unusual intrinsic currents in mitral cells and dendrodendritic inhibitory synaptic connections that mediate the strong lateral interactions between different subpopulations of mitral cells. This proposal examines the cellular mechanisms that underlie both the unusual intrinsic properties of olfactory bulb neurons and the dendrodendritic inhibitory circuits that underlie recurrent and lateral inhibition. We employ a combination of intracellular recording and neuropharmacological tools to investigate why recurrent inhibition in the olfactory bulb appears to be dependent upon NMDA receptors and how it is modulated by cholinergic receptors. We also have discovered a new class of interneurons in the olfactory bulb that become persistently active following transient stimuli. We propose experiments to define the intracellular signaling mechanisms that mediate and modulate persistent activity. Finally, we propose a series of experiments to determine how mitral cells integrate these different synaptic and intrinsic currents when generating physiological discharge patterns. Understanding how sensory information is represented as spatio-temporal discharge patterns will have wide ranging significance beyond the immediate goal of understanding the synaptic organization of the olfactory bulb. Electrical stimulation of different CNS regions has been shown to be therapeutic in neurological disease. Currently, these interventions are based on empirical findings, often employing non-physiological tetanic stimulus trains, rather than patterned stimuli at physiological frequencies. One (1) outcome from the present study is likely to be a better understanding of how physiological patterns of activity are generated by local circuits. Our work may lead to new therapeutic strategies for treating neurological diseases such as Parkinson's disease and epilepsy that employ biologically-inspired patterned stimulus trains.

描述（由申请人提供）：在最基本的水平上，中枢神经系统参与处理由个体神经细胞中动作电位的时间模式表示的信息。嗅觉系统是研究感觉信息如何编码的理想大脑区域。虽然嗅觉传导发生在专门的嗅觉受体神经元，产生时间调制的气味特异性神经放电的实际工作开始于嗅球。在这里，来自受体神经元的简单单调输入激活了空间定义的输出神经元（二尖瓣细胞）的亚群。然而，二尖瓣细胞并不简单地将感觉信息传递到三级大脑区域。相反，受体神经元的输入与不寻常的内在电流在二尖瓣细胞和树突状抑制性突触连接，介导的强大的横向相互作用之间的二尖瓣细胞的不同亚群相互作用。该建议探讨了嗅球神经元的不寻常的内在特性和树突状抑制电路的基础上，反复和侧抑制的细胞机制。我们采用细胞内记录和神经药理学工具相结合，以调查为什么在嗅球复发性抑制似乎是依赖于NMDA受体，以及它是如何调制胆碱能受体。我们还在嗅球中发现了一类新的中间神经元，它们在短暂刺激后变得持续活跃。我们提出实验来定义介导和调节持续活性的细胞内信号传导机制。最后，我们提出了一系列的实验，以确定如何二尖瓣细胞整合这些不同的突触和内在电流时，产生生理放电模式。了解感觉信息是如何表现为时空放电模式将有广泛的意义，超越了理解嗅球的突触组织的直接目标。不同CNS区域的电刺激已被证明在神经系统疾病中是治疗性的。目前，这些干预措施是基于经验的发现，往往采用非生理强直刺激列车，而不是在生理频率的模式刺激。本研究的结果之一可能是更好地理解局部回路如何产生生理活动模式。我们的工作可能会导致新的治疗策略，用于治疗神经系统疾病，如帕金森病和癫痫，采用生物启发的模式化刺激列车。