Balancing Excitation and Inhibition within Olfactory Bulb Glomeruli

平衡嗅球肾小球内的兴奋和抑制

• 批准号: 8594098
• 负责人: Joseph Donald Zak
• 金额: $ 3.34万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594098
• 关键词: Abbreviations; Acute; Address; Affect; Afferent Neurons; Affinity; Alzheimer' s Disease; Axon; Binding; Biological; Brain; Cells; Detection; Diagnostic; Disease; Effectiveness; Electrophysiology (science); Equilibrium; Etiology; Exhibits; Figs - dietary; Functional disorder; Glutamates; Image; Juxtaglomerular Cell; Label; Ligands; Measures; Metabotropic Glutamate Receptors; Modeling; Nasal Epithelium; Neurodegenerative Disorders; Neurons; Odorant Receptors; Odors; Olfactory Nerve; Outcome; Output; Parkinson Disease; Patients; Pattern; Pharmacology; Population; Population Analysis; Probability; Property; Proteins; Rattus; Resistance; Role; Schizophrenia; Sensory; Signal Transduction; Slice; Source; Structure; Symptoms; Synapses; System; Techniques; Testing; Therapeutic; Transgenic Organisms; Translating; Venus; base; excitatory neuron; gamma-Aminobutyric Acid; imaging modality; inhibitory neuron; insight; neural circuit; neuropsychiatry; neuroregulation; neurotransmitter release; novel; olfactory bulb; promoter; public health relevance; receptor; research study; vesicular GABA transporter

DESCRIPTION (provided by applicant): Sensory input in the mammalian olfactory bulb arises from olfactory sensory neurons located within the nasal epithelium that project their axons to distinct networks known as glomeruli, each corresponding to a unique feature of an odorant molecule. A biological limitation of the olfactory system is the inability of odorant receptors located on olfactory sensory neurons to be perfectly selective. Odorant receptors have a "preferred" ligand, although they may also bind additional ligands across a spectrum of affinities. The ability of odorant receptors to bind both "preferred" and "non-preferred" ligands could obscure the brain's interpretation of the actual ligand present. I propose that this problem is addressed mainly through the activation of the local network of neurons that surround glomeruli. These cells, which include glutamatergic external tufted (ET) cells and GABAergic periglomerular (PG) cells, act as a signal detection mechanism, selectively filtering out weak signals in favor of strong signals. Aim 1 will examine the possibility that PG cells and ET cells are activated by varying degrees of sensory input, allowing for low-level olfactory input to selectively activate inhibitory PG cells, thus effectively filtering weak sensory input signals. Ai 2 explores whether PG cell activity can be modulated by local glutamate released from ET cells, which may increase the effectiveness of weak signals and produce temporal patterning in glomerular activity. Aim 3 tests the ability of the ET cell-PG cell microcircuit to control the probability of mitral cell activation and also employs a novel population analysis that allows for identification of excitatory and inhibitory neurons in the glomerular layer of the olfactory bulb. This proposal examines a model for intra-glomerular interactions in which PG cells "gate" glomerular activation.

描述（由申请人提供）：哺乳动物嗅球中的感觉输入来自位于鼻上皮内的嗅觉感觉神经元，这些神经元将轴突投射到称为肾小球的不同网络，每个网络对应于气味分子的独特特征。嗅觉系统的生物学限制是位于嗅觉感觉神经元上的气味受体无法完全选择性。气味受体具有“优选”配体，尽管它们也可以在一系列亲和力上结合其他配体。 气味受体结合“首选”和“非首选”配体的能力可能会模糊大脑对实际存在的配体的解释。我认为这个问题主要通过激活肾小球周围神经元的局部网络来解决。这些细胞包括谷氨酸能外部簇绒 (ET) 细胞和 GABA 能球周 (PG) 细胞，充当信号检测机制，选择性地滤除弱信号以支持强信号。目标1将检验PG细胞和ET细胞被不同程度的感觉输入激活的可能性，允许低水平的嗅觉输入选择性地激活抑制性PG细胞，从而有效过滤微弱的感觉输入信号。 Ai 2 探索 PG 细胞活性是否可以通过 ET 细胞释放的局部谷氨酸进行调节，这可能会增加弱信号的有效性并产生肾小球活性的时间模式。 Aim 3 测试了 ET 细胞-PG 细胞微电路控制二尖瓣细胞激活概率的能力，并采用了一种新颖的群体分析，可以识别嗅球肾小球层中的兴奋性和抑制性神经元。该提案研究了肾小球内相互作用的模型，其中 PG 细胞“门控”肾小球激活。