嗅球对嗅觉信息的处理

哺乳动物的嗅觉系统拥有惊人的能力,它可以识别和分辨成千上万种分子结构各异的气味分子。这种识别能力是由基因决定的。近年来,分子生物学和神经生理学的研究使得我们对嗅觉识别的分子基础和嗅觉系统神经连接的认识有了质的飞跃。气味分子的识别是由一千多种气味受体完成的,鼻腔中的嗅觉感觉神经元表达这些气味受体基因。每个感觉神经元只表达一种气味受体基因。表达同种气味受体的感觉神经元投射到嗅球表面的一个或几个嗅小球中,从而在嗅球中形成一个精确的二维连接图谱。了解嗅球对气味信息的加工和处理方式是我们研究嗅觉系统信号编码的一个重要环节。文章概述并总结了有关嗅球信号处理的最新研究成果。     

Profound context-dependent plasticity of mitral cell responses in olfactory bulb

On the basis of its primary circuit it has been postulated that the olfactory bulb (OB) is analogous to the retina in mammals. In retina, repeated exposure to the same visual stimulus results in a neural representation that remains relatively stable over time, even as the meaning of that stimulus to the animal changes. Stability of stimulus representation at early stages of processing allows for unbiased interpretation of incoming stimuli by higher order cortical centers. The alternative is that early stimulus representation is shaped by previously derived meaning, which could allow more efficient sampling of odor space providing a simplified yet biased interpretation of incoming stimuli. This study helps place the olfactory system on this continuum of subjective versus objective early sensory representation. Here we show that odor responses of the output cells of the OB, mitral cells, change transiently during a go–no-go odor discrimination task. The response changes occur in a manner that increases the ability of the circuit to convey information necessary to discriminate among closely related odors. Remarkably, a switch between which of the two odors is rewarded causes mitral cells to switch the polarity of their divergent responses. Taken together these results redefine the function of the OB as a transiently modifiable (active) filter, shaping early odor representations in behaviorally meaningful ways.     

Neurally Encoding Time for Olfactory Navigation

Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal’s ability to locate the source of odor cues in realistic turbulent environments—a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing.     

The olfactory glomerulus: A cortical module with specific functions

The axons of many olfactory receptor cells converge on an individual glomerulus in the olfactory bulb, where they make contacts with the distal dendrites of mitral and tufted cells. Each glomerulus is targeted by olfactory receptor neurons expressing a single type of olfactory receptor protein. The glomerulus provides a unique model in which the function of a cortical module can be unambiguously established. Here we review the increasing evidence that a key functional operation of the glomerulus is to act as a signal-to-noise enhancing device in the processing of sensory input and that this function is critical across vertebrate and invertebrate species for the ability to detect specific odor stimuli within “noisy” odor environments and to carry out discriminations between odor molecules that are structurally closely related.     

A cyclic nucleotide-gated channel in the brain regulates olfactory modulation through neuropeptide F in fruit fly Drosophila melanogaster

Olfactory sensing and its modulation are important for the insects in recognizing diverse odors from the environment and in making correct decisions to survive. Identifying new genes involved in olfactory modulation and unveiling their mechanisms may lead us to understand decision making processes in the central nervous system. Here, we report a novel olfactory function of the cyclic nucleotide-gated (CNG) channel CG42260 in modulating ab3A olfactory sensory neurons, which specifically respond to food-derived odors in fruit fly Drosophila melanogaster. We found that two independent CG42260 mutants show reduced responses in the ab3A neurons. Unlike mammalian CNGs, CG42260 is not expressed in the odorant sensory neurons but broadly in the central nervous system including neuropeptide-producing cells. By using molecular genetic tools, we identified CG42260 expression in one pair of neuropeptide F (NPF) positive L1-l cells known to modulate food odor responsiveness. Knockdown of CG42260 in the NPF neurons reduced production of NPF in Ll-1 cells, which in turn, led to reduction of neuronal responses of the ab3A neurons. Our findings show the novel biological function of CG42260 in modulating olfactory responses to food odor through NPF.     

Cortical feedback and gating in odor discrimination and generalization

A central question in neuroscience is how context changes perception. In the olfactory system, for example, experiments show that task demands can drive divergence and convergence of cortical odor responses, likely underpinning olfactory discrimination and generalization. Here, we propose a simple statistical mechanism for this effect based on unstructured feedback from the central brain to the olfactory bulb, which represents the context associated with an odor, and sufficiently selective cortical gating of sensory inputs. Strikingly, the model predicts that both convergence and divergence of cortical odor patterns should increase when odors are initially more similar, an effect reported in recent experiments. The theory in turn predicts reversals of these trends following experimental manipulations and in neurological conditions that increase cortical excitability.     

Local neurons play key roles in the mammalian olfactory bulb

Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in understanding the general neural mechanisms involved in both sensory perception and memory. Due to space constraints, this review focuses exclusively on the olfactory systems of vertebrates and primarily those of mammals.     

Negatively calcium-modulated membrane guanylate cyclase signaling system in the rat olfactory bulb

The mechanism by which the individual odor signals are translated into the perception of smell in the brain is unknown. The signal processing occurs in the olfactory system which has three major components: olfactory neuroepithelium, olfactory bulb, and olfactory cortex. The neuroepithelial layer is composed of ciliated sensory neurons interspersed among supportive cells. The sensory neurons are the sites of odor transduction, a process that converts the odor signal into an electrical signal. The electrical signal is subsequently received by the neurons of the olfactory bulb, which process the signal and then relay it to the olfactory cortex in the brain. Apart from information about certain biochemical steps of odor transduction, there is almost no knowledge about the means by which the olfactory bulb and cortical neurons process this information. Through biochemical, functional, and immunohistochemical approaches, this study shows the presence of a Ca(2+)-modulated membrane guanylate cyclase (mGC) transduction system in the bulb portion of the olfactory system. The mGC is ROS-GC1. This is coexpressed with its specific modulator, guanylate cyclase activating protein type 1 (GCAP1), in the mitral cells. Thus, a new facet of the Ca(2+)-modulated GCAP1--ROS-GC1 signaling system, which, until now, was believed to be unique to phototransduction, has been revealed. The findings suggest a novel role for this system in the polarization and depolarization phenomena of mitral cells and also contradict the existing belief that no mGC besides GC-D exists in the olfactory neurons.     

The loss of scents: Do defects in olfactory sensory neuron development underlie human disease?

The olfactory system is a fascinating and beguiling sensory system: olfactory sensory neurons detect odors underlying behaviors essential for mate choice, food selection, and escape from predators, among others. These sensory neurons are unique in that they have dendrites contacting the outside world, yet their first synapse lies in the central nervous system. The information entering the central nervous system is used to create odor memories that play a profound role in recognition of individuals, places, and appropriate foods. Here, the structure of the olfactory epithelium is given as an overview to discuss the origin of the olfactory placode, the plasticity of the olfactory sensory neurons, and finally the origins of the gonadotropin‐releasing hormone neuroendocrine cells. For the purposes of this review, the development of the peripheral sensory system will be analyzed, incorporating recently published studies highlighting the potential novelties in development mechanisms. Specifically, an emerging model where the olfactory epithelium and olfactory bulb develop simultaneously from a continuous neurectoderm patterned at the end of gastrulation, and the multiple origins of the gonadotropin‐releasing hormone neuroendocrine cells associated with the olfactory sensory system development will be presented. Advances in the understanding of the basic mechanisms underlying olfactory sensory system development allows for a more thorough understanding of the potential causes of human disease. Birth Defects Research (Part C) 105:114–125, 2015. © 2015 Wiley Periodicals, Inc.     

昆虫气味认知的嗅觉神经结构及分子机制

大多数昆虫主要通过气味认知感知外界环境的变化,维持生命活动。探究昆虫气味认知的嗅觉系统神经结构及分子机制,对于完善气味认知神经生物学理论及利用其原理进行仿生学研究等有重要的科学意义。近年,关于昆虫气味认知科学研究有了很大的进展。本文从昆虫神经生物学的视角详细综述了近年关于昆虫气味认知的嗅觉神经结构、分子机制及气味信号的神经传导途径等方面的基本理论及最新研究成果。综述结果显示:昆虫对气味的认知是通过嗅觉神经系统的触角感器、触角叶(AL)、蕈形体(MB)等脑内多层信号处理神经结构来实现的。当外界气味分子进入触角感器内后,由感器内特定的气味识别蛋白(OBP)将气味分子运载到达嗅觉感受神经元(ORN)树突膜上的受体位点,气味分子与表达特定气味的受体(OR)结合产生电信号,并以动作电位的形式通过ORN的轴突传到脑内的触角叶。在触角叶经过嗅觉纤维球对气味信息选择性加工处理,再由投射神经元(PNs)将初步的识别和分类的气味信息传到蕈形体和外侧角(LH)等神经中枢,实现对气味的识别和认知。虽然,近年昆虫气味认知神经生物学的研究有了很大的进步,但是,我们认为目前的研究成果还不能完全阐明昆虫气味认知的神经机制,还有很多问题,例如,触角叶上众多的嗅觉纤维球是如何对嗅觉感受神经元传入的气味信息进行编码处理的?等有待进一步深入研究。为了搞清这些疑难问题,我们认为需要提高现有的实验技术水平,加强电生理学和分子神经生物学相结合的实验研究,从分子水平探究气味认知的神经机制可能是未来研究的热点。     

Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb

The olfactory system shares many principles of functional organization with other sensory systems, but differs in that the sensory input is in the form of molecular information carried in odor molecules. Current studies are providing new insights into how this information is processed. In analogy with the spatial receptive fields of visual neurons, the molecular receptive range of olfactory cells is defined as the range of odor molecules that will affect the firing of that cell. Olfactory receptor molecules belong to a large gene family; it is hypothesized that individual receptor molecule may have relatively broad molecular receptive ranges, and that an individual receptor cell need therefore express only one or a few different types of receptors to cover a broad range. Mitral/tufted cells have narrower molecular receptive ranges, comprising molecules with related structures (odotopes). This is believed to reflect processing through the olfactory glomeruli, each glomerulus acting as a convergence center for related inputs. Varying overlapping specificities of receptor cells, glomeruli and mitral/tufted cells appear to provide the basis for discrimination of odor molecules, in analogy with discrimination of color in the visual systems.     

Transplant Antennae and Host Brain Interact to Shape Odor Perceptual Space in Male Moths

Behavioral responses to odors rely first upon their accurate detection by peripheral sensory organs followed by subsequent processing within the brain’s olfactory system and higher centers. These processes allow the animal to form a unified impression of the odor environment and recognize combinations of odorants as single entities. To investigate how interactions between peripheral and central olfactory pathways shape odor perception, we transplanted antennal imaginal discs between larval males of two species of moth Heliothis virescens and Heliothis subflexa that utilize distinct pheromone blends. During metamorphic development olfactory receptor neurons originating from transplanted discs formed connections with host brain neurons within olfactory glomeruli of the adult antennal lobe. The normal antennal receptor repertoire exhibited by males of each species reflects the differences in the pheromone blends that these species employ. Behavioral assays of adult transplant males revealed high response levels to two odor blends that were dissimilar from those that attract normal males of either species. Neurophysiological analyses of peripheral receptor neurons and central olfactory neurons revealed that these behavioral responses were a result of: 1. the specificity of H. virescens donor olfactory receptor neurons for odorants unique to the donor pheromone blend and, 2. central odor recognition by the H. subflexa host brain, which typically requires peripheral receptor input across 3 distinct odor channels in order to elicit behavioral responses.     

Olfactory networks: from sensation to perception

Olfactory networks, comprised of sensory neurons and interneurons, detect and process changes in the chemical environment to drive animal behavior. Recent studies combining genetics with behavioral analyses and imaging in worms, flies and mice have revealed new insights into the mechanisms of olfaction. In this discussion, we focus on three interesting findings. First, sensory neuron responses to odor are modulated by neuropeptides. This modulation might serve to extend the range of responses of the sensory neurons and also to integrate internal state information into the chemosensory circuit. Second, genetic tracing studies in mice and flies have shown that the first layer of connections in chemosensory circuits from olfactory epithelium to the glomeruli are stereotyped, while the subsequent connections to higher order sensory processing regions are not. Distributed connectivity to the higher order sensory processing regions has profound implications for how odors are represented in those regions. Third, recent work has revealed that odors are surprisingly sparsely represented in the piriform cortex. The sparse coding in the higher brain centers implies a much greater role for experience and learning in mediating responses to olfactory cues. Analyzing olfactory network function in various species provides us with fascinating clues about how sensory information is acquired, processed and represented at multiple levels within the nervous system.     

The sensory basis of olfactory search behavior in banded kokopu (<Emphasis Type="Italic">Galaxias fasciatus</Emphasis>)

The sensory basis of olfactory search behavior was investigated in the banded kokopu, Galaxias fasciatus, using a flow tank. In the presence of a 2 cm s(-1) current flow, banded kokopu use both water current and chemical information to locate a food odor source. The superficial neuromasts of the lateral line system mediate the rheotactic component of the odor search. A physical block of one olfactory nostril did not affect the olfactory search strategy employed by banded kokopu in still water or in the presence of a current flow. Thus, there is no evidence that banded kokopu perform a bilateral comparison of the olfactory stimulus during their odor search. Previously, olfaction and gustation have been the only sensory systems shown to directly mediate orientation and movement towards odor sources in fish. The use of hydrodynamic cues by fish in location of an olfactory source has been previously proposed, but without direct experimental identification of the sensory systems employed. This study identifies the contributing roles of both olfactory and hydrodynamic sensory systems to the olfactory search repertoire of fish.     

Presynaptic modulation of early olfactory processing in Drosophila

Most animals are endowed with an olfactory system that is essential for finding foods, avoiding predators, and locating mating partners. The olfactory system must encode the identity and intensity of behaviorally relevant stimuli in a dynamic environmental landscape. How is olfactory information represented? How is a large dynamic range of odor concentrations represented in the olfactory system? How is this representation modulated to meet the demands of different internal physiological states? Recent studies have found that sensory terminals are important targets for neuromodulation. The emerging evidence suggests that presynaptic inhibition scales with sensory input and thus provides a mechanism to increase dynamic range of odor representation. In addition, presynaptic facilitation could be a mechanism to alter behavioral responses in hungry animals. This review will focus on the GABA(B) (gamma-aminobutyric acid) receptor-mediated presynaptic inhibition, and neuropeptide-mediated presynaptic modulation in Drosophila.     

Adjusting neurophysiological computations in the adult olfactory bulb

The olfactory bulb receives signals from olfactory sensory neurons and conveys them to higher centers. The mapping of the sensory inputs generates a reproducible spatial pattern in the glomerular layer of the olfactory bulb for each odorant. Then, this restricted activation is transformed into highly distributed patterns by lateral interactions between relay neurons and local interneurons. Thus, odor information processing requires the spatial patterning of both sensory inputs and synaptic interactions. In other words, odor representation is highly dynamic and temporally orchestrated. Here, we describe how the local inhibitory network shapes the global oscillations and the precise synchronization of relay neurons. We discuss how local inhibitory interneurons transpose the spatial dimension into temporal patterning. Remarkably, this transposition is not fixed but highly flexible to continuously optimize olfactory information processing.     

Making scents of olfactory neurogenesis.

Olfaction was long considered to belong more to the realm of art than to that of science. As a result, how the brain perceives, discriminates, and recognizes odorant molecules is still a mystery. Recent progress has nonetheless been made at early stages of the olfactory pathway when olfactory studies entered into the molecular era to elucidate the first contact of an odor molecule with a receptor. Our group focuses on the analysis of odor information in the olfactory bulb, the first processing relay in the mammalian brain. Using this model, we are attempting to decipher the code for odorant information. Furthermore, the olfactory bulb also provides an attractive model to investigate neuronal proliferation, differentiation, migration, and neuronal death, processes involving an interplay between genetic and epigenetic influences. Finally, our goal is to explore the possible consequences of the olfactory bulb plasticity, in olfactory performance. For these purposes, we aim to combine morphological, electrophysiological and behavioral approaches to investigate: (1) how the olfactory bulb processes odor molecule information, (2) how neural precursors differentiate into olfactory bulb interneurons, (3) how these newly-generated neurons integrate into an operational neural network, (4) what role they play in the adult olfactory bulb, and (5) how are basic olfactory functions maintained in such a sensory system subjected to continuous renewal of a large percentage of its neuronal population. These questions should provide new fuel for the molecular and cellular bases of sensory perception and shed light onto cellular bases of learning and memory.     

Lessons from snail tentacles

The olfactory system of the snail is functionally capable andstructurally complex. The morphology of the olfactory epitheliumand the glomeruli are similar to analogous structures in vertebrates.However, the snail system differs markedly from the vertebratesystem in its lack of a mucus secretion and the apparent absenceof spatial patterning. Such similarities and differences teachus about the limitations and options governing the evolutionof olfactory systems. The comparative approach leads to thefollowing conclusions, or ‘lessons’: (1) Death andreplacement is normal for olfactory receptors. (2) Olfactionrequires large numbers of receptors and other neurons. (3) Glomerularstructures in the olfactory neuropil aid sensory processing.(4) Local interactions are important in the early stages ofolfactory processing. (5) The role of mucus in olfaction ispeculiar to the vertebrate nose. (6) The spatial patterningof odor responses is not necessary for effective odor processing.     

A physicochemical model of odor sampling

We present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling. The outcome of these competing ligand-receptor interactions yields a pattern of receptor activation levels, thereafter mapped to glomerular presynaptic activation levels based on the convergence of sensory neuron axons. The metric of greatest interest is the mean discrimination sensitivity, a measure of how effectively the olfactory system at this level is able to recognize a small change in the physicochemical quality of a stimulus. This model presents several significant outcomes, both expected and surprising. First, adding additional receptors reliably improves the system’s discrimination sensitivity. Second, in contrast, adding additional ligands to an odorscene initially can improve discrimination sensitivity, but eventually will reduce it as the number of ligands increases. Third, the presence of antagonistic ligand-receptor interactions produced clear benefits for sensory system performance, generating higher absolute discrimination sensitivities and increasing the numbers of competing ligands that could be present before discrimination sensitivity began to be impaired. Finally, the model correctly reflects and explains the modest reduction in odor discrimination sensitivity exhibited by transgenic mice in which the specificity of glomerular targeting by primary olfactory neurons is partially disrupted.     

Cortical contributions to olfaction: plasticity and perception

In most sensory systems, the sensory cortex is the place where sensation approaches perception. As described in this review, olfaction is no different. The olfactory system includes both primary and higher order cortical regions. These cortical structures perform computations that take highly analytical afferent input and synthesize it into configural odor objects. Cortical plasticity plays an important role in this synthesis and may underlie olfactory perceptual learning. Olfactory cortex is also involved in odor memory and association of odors with multimodal input and contexts. Finally, the olfactory cortex serves as an important sensory gate, modulating information throughput based on recent experience and behavioral state.