生物谷报道:2007年8月16日,北京生命科学研究所罗敏敏实验室在《Science》杂志上发表文章报道了小鼠可以通过一类特殊的嗅觉神经元感受接近于空气中浓度的二氧化碳。
二氧化碳(CO2)对于许多生物是一种重要的环境信号分子。传统上二氧化碳被认为是无色无味的气体。经典的心理物理学测试证明对于二氧化碳确实不能由人类的嗅觉系统所检测,但是其他的哺乳动物是否可以通过嗅觉系统感受低浓度的二氧化碳(空气中二氧化碳平均浓度0.038%)仍然不清楚。
由北京生命科学研究所罗敏敏研究员所领导的课题组运用分子生物学、免疫组织化学、小鼠遗传操作、电生理、钙成像、以及行为学等多种实验手段,证明了小鼠能通过一类表达D型鸟苷酸环化酶(GC-D)的嗅觉感觉细胞感受接近于大气中浓度的二氧化碳。他们首先发现表明碳酸酐酶II,一种催化CO2与水生成HCO3-和H+的酶,特异地表达在这类GC-D神经元中。这些神经元的轴突投射到嗅球中的项链嗅小球,形成所谓的项链嗅觉系统。这一研究运用钙成像与电生理记录表明CO2激活GC-D神经元以及嗅球中与项链嗅小球联系的神经细胞。行为学实验结果表明小鼠检测CO2的阈限为0.066%,非常接近空气中CO2的平均浓度(0.038%)。最后,他们的药理实验及行为实验证明小鼠这样灵敏的二氧化碳检测能力需要碳酸酐酶II的活性及环鸟苷酸环敏感的离子通道的开发。
这一研究首次证明二氧化碳可以被哺乳动物的嗅觉系统灵敏地检测到,并且此一检测是通过项链嗅觉系统所完成,而此一特异的嗅觉系统的功能一直不清楚。最后,此一研究对于哺乳动物对CO2检测的细胞机制提供了初步线索。
Fig. 1. CAII immunoreactivity in GC-D+ neurons and necklace glomeruli. (A) Bilaterally symmetric distribution of CAII+ cells (arrows) in the OE. (B) High-power view of CAII immunoreactivity in a CAII+ cluster. (C) PDE2A immunoreactivity in the same section as (B). (D) Overlay of (B) and (C). (E) Acoronal section of the caudal OB showing CAII+ glomeruli (arrows) with largely bilateral symmetry. (F) High-power view of CAII immunoreactivity within the dashed box in (E). (G) PDE2A immunoreactivity. (H) Overlay of (F) and (G). Blue, DAPI labeling. (I to K) CAII expression overlaps with GFP labeling in the OE of GCD-ITG mice. (I) CAII immunoreactivity. (J) GFP immunoreactivity within the same region as (I). (K) Overlay of (I) and (J). (L to N) CAII expression overlaps with GFP labeling in the OB of GCD-ITG mice. (L) CAII+ glomeruli. (M) GFP+ glomeruli within the same region as (L). (N) Overlay of (L) and (M). Scale bars in (B), 20 µm; (F), 100 µm; (I), 10 µm; and (L), 50 µm. [View Larger Version of this Image (368K JPEG file)]
原文出处:
Science 17 August 2007 Vol 317, Issue 5840
Detection of Near-Atmospheric Concentrations of CO2 by an Olfactory Subsystem in the Mouse
Ji Hu, Chun Zhong, Cheng Ding, Qiuyi Chi, Andreas Walz, Peter Mombaerts, Hiroaki Matsunami, and Minmin Luo
Science 17 August 2007: 953-957.
Mice can sense near-atmospheric concentrations of CO2 using a subset of olfactory neurons that may utilize the catabolic enzyme carbonic anhydrase.
Abstract »| Full Text »| PDF »| Supporting Online Material »|
作者简介:
Dr. Minmin Luo’s Lab
Minmin Luo,Ph.D
Assistant Investigator, NIBS, Beijing, China
Research Description:
Our lab is focusing on two related neurobiology questions:
1. the encoding of olfactory signals in the mammalian brain;
2. the physiological mechanisms of innate social behaviors at the level of neural circuits.
Mammals can detect and discriminate infinite number of odorant chemicals. Over the last decade, dramatic progresses have been achieved in our understanding of the olfactory system. The work by Buck and Axel revealed that mammals possess over 1000 odorant receptors. Each olfactory sensory neuron expresses a single odorant receptor, and neurons of common receptors converge into one or two glomeruli in the the olfactory bulb, thus forming a topographic map at the level of odorant receptor. However, it remains unclear how odorants are encoded by the olfactory bulb. Our laboratory studies how neuronal activity in the olfactory bulb encode olfactory signals and then project to downstream stations, using approaches such as electrophysiology, optical imaging, and genetic engineering.
Some special odorants, such as the body odorants emanated by other conspecifics or predators, can be detected at especially low concentrations and effectively release specific behaviors, such as mating, aggression, or innate fears. A discrete neural pathway from the olfactory bulb to the hypothalamus via the medial amygdala detects these odorants and regulates the innate social behaviors. We are using approaches including electrophysiology, neural tract tracing, genetic engineering, and behavioral assay to study the representation of the olfactory signals in this pathway. We are testing the labeled-line hypothesis: whether some specialized receptor neurons and their directly connected central pathways respond selectively to subset of social signals and regulate specific behavior. We are also recording the intrinsic and synaptic properties of the neurons in this pathway from slice preparations to examine the physiological substrates for the representation of social signals. Many mental diseases manifest themselves as disorders of social behavior. Our studies thus not only have the potentials of contributing to the basic understanding of sensory processing and some most fundamental forms of social behaviors but also may facilitate clinical efforts toward the cure of these diseases.
Publications:
1. Luo M. and Katz L.C.. Encoding Pheromones by the Mammalian Vomeronasal System. Curr Opinion Neurobiol. 2004; 14:428-34.
2. Luo M.. Got milk? A pheromonal message for newborn rabbits. Bioessays. 2004; 26:6-9.
3. Luo M., Fee M.S., and Katz L.C.. Encoding pheromonal signals in the accessory olfactory bulb of behaving mice. Science. 2003; 299:1196-1201 (full research article featured with cover and News and Views).
4. Luo M. and Perkel D.J.. Intrinsic properties and synaptic input for neurons within an avian motor thalamic nucleus during the phase crucial for song learning. J Neurophysiol. 2002; 88:1903-1914.
5. Perkel D.J., Farries M.A., Luo M., and Ding L. Electrophysiological analysis of a songbird basal ganglia circuit essential for vocal plasticity. Brain Res Bulletin. 2002; 57:529-532 (Invited review).
6. Luo M. and Katz L.C.. Response correlation maps of neurons in the mammalian olfactory bulb. Neuron. 2001; 32:1165-1179.
7. Luo M., Ding L., and Perkel D.J.. An avian basal ganglia pathway essential forvocal learning nucleus in the zebra finch song system forms closed topographic loops. J Neurosci. 2001; 21:6836-45.
8. Luo, M., and Perkel, D.J. (1999) A GABAergic, strongly inhibitory projection to a thalamic nucleus in the zebra finch song system. J Neurosci. 19(15):6700-11.
9. Luo, M., and Perkel, D.J. (1999) Long-range GABAergic projection in a circuit essential for vocal learning. J Comp Neurol 403: 68-84.
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