Balancing Excitation and Inhibition within Olfactory Bulb Glomeruli

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，所述嗅觉感觉神经元将其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。嗅觉系统的一个生物学限制是位于嗅觉感觉神经元上的气味受体不能具有完全的选择性。气味剂受体具有“优选的”配体，尽管它们也可以在一系列亲和力中结合另外的配体。 气味受体结合“偏好”和“非偏好”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是通过激活肾小球周围的局部神经元网络来解决的。这些细胞，包括谷氨酸能外部簇状（ET）细胞和GABA能肾小球周围（PG）细胞，作为一种信号检测机制，选择性地过滤掉弱信号，有利于强信号。目的1将研究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，从而有效地过滤弱的感觉输入信号。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来调节，这可能会增加弱信号的有效性，并在肾小球活动中产生时间模式。目的3测试ET细胞-PG细胞微电路控制二尖瓣细胞激活的概率的能力，并且还采用了一种新的群体分析，其允许识别嗅球的肾小球层中的兴奋性和抑制性神经元。该建议探讨了一个模型，肾小球内的相互作用，PG细胞“门”肾小球激活。

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.