Responses of vomeronasal neurons to natural stimuli

The vomeronasal organ (VNO) of mammals plays an essential role in the detection of pheromones. We obtained simultaneous recordings of action potentials from large subsets of VNO neurons. These cells responded to components of urine by increasing their firing rate. This chemosensory activation required phospholipase C function. Unlike most other sensory neurons, VNO neurons did not adapt under prolonged stimulus exposure. The full time course of the VNO spiking response is captured by a simple quantitative model of ligand binding. Many individual VNO neurons were strongly selective for either male or female mouse urine, with the effective concentrations differing as much as a thousandfold. These results establish a framework for understanding sensory coding in the vomeronasal system.     

Encoding pheromonal signals in the accessory olfactory bulb of behaving mice

Many mammalian species rely on pheromones-semiochemicals produced by other members of the same species-to communicate social status and reproductive readiness. To assess how the central nervous system integrates the complex repertoire of pheromones, we recorded from single neurons in the accessory olfactory bulb, a nucleus that processes pheromonal signals, of male mice engaged in natural behaviors. Neuronal firing was robustly modulated by physical contact with male and female conspecifics, with individual neurons activated selectively by specific combinations of the sex and strain of conspecifics. We infer that mammals encode social and reproductive information by integrating vomeronasal sensory activity specific to sex and genetic makeup.     

Defective presentation of endogenous antigen by a cell line expressing class I molecules

Cytotoxic T lymphocytes (CTLs) recognize class I major histocompatibility complex (MHC) molecules associated with antigenic peptides derived from endogenously synthesized proteins. Binding to such peptides is a requirement for class I assembly in the endoplasmic reticulum (ER). A mutant human cell line, T2, assembles and transports to its surface some, but not all, class I MHC molecules. The class I molecules expressed on the surface of T2 do not present peptides derived from cytosolic antigens, although they can present exogenously added peptides to CTL. The transported class I molecules may interact weakly with an unknown retaining factor in the ER such that they can assemble despite the relative shortage of peptides.     

Loss of sex discrimination and male-male aggression in mice deficient for TRP2

The mouse vomeronasal organ (VNO) is thought to mediate social behaviors and neuroendocrine changes elicited by pheromonal cues. The molecular mechanisms underlying the sensory response to pheromones and the behavioral repertoire induced through the VNO are not fully characterized. Using the tools of mouse genetics and multielectrode recording, we demonstrate that the sensory activation of VNO neurons requires TRP2, a putative ion channel of the transient receptor potential family that is expressed exclusively in these neurons. Moreover, we show that male mice deficient in TRP2 expression fail to display male-male aggression, and they initiate sexual and courtship behaviors toward both males and females. Our study suggests that, in the mouse, sensory activation of the VNO is essential for sex discrimination of conspecifics and thus ensures gender-specific behavior.     

Amygdaloid nucleus: new afferent input from the vomeronasal organ

Terminal degeneration stained by the Fink-Heimer technique was found in the medial and cortical amygdaloid nuclei in a discrete zone after lesions were inflicted in the accessory olfactory bulb but not after lesions were made in the main olfactory bulb in the rabbit. Since the accessory olfactory bulb receives the endings of the vomeronasal nerve, the mediocortical complex of the amygdala is the central projection area for the vomeronasal sensory organ. The vomeronasal organ is seen as having new potential significance in sexual and feeding behavior because the cortical amygdaloid nucleus projects to the anterior, medial hypothalamus and the ventromedial nucleus.     

Constitutive display of cryptic translation products by MHC class I molecules

Major histocompatibility complex (MHC) class I molecules display tens of thousands of peptides on the cell surface, derived from virtually all endogenous proteins, for inspection by cytotoxic T cells (CTLs). We show that, in normal mouse cells, MHC I molecules present a peptide encoded in the 3' "untranslated" region. Despite its rarity, the peptide elicits CTL responses and induces self-tolerance, establishing that immune surveillance extends well beyond conventional polypeptides. Furthermore, translation of this cryptic peptide occurs by a previously unknown mechanism that decodes the CUG initiation codon as leucine rather than the canonical methionine.     

Encoding gender and individual information in the mouse vomeronasal organ

The mammalian vomeronasal organ detects complex chemical signals that convey information about gender, strain, and the social and reproductive status of an individual. How these signals are encoded is poorly understood. We developed transgenic mice expressing the calcium indicator G-CaMP2 and analyzed population responses of vomeronasal neurons to urine from individual animals. A substantial portion of cells was activated by either male or female urine, but only a small population of cells responded exclusively to gender-specific cues shared across strains and individuals. Female cues activated more cells and were subject to more complex hormonal regulations than male cues. In contrast to gender, strain and individual information was encoded by the combinatorial activation of neurons such that urine from different individuals activated distinctive cell populations.     

Limit of T cell tolerance to self proteins by peptide presentation

Cytotoxic T lymphocytes (CTLs) recognize foreign peptides bound to major histocompatibility complex (MHC) class I molecules. MHC molecules can also bind endogenous self peptides, to which T cells are tolerant. Normal mice contained CTLs specific for self peptides that were from proteins of ubiquitous or tissue-restricted expression. In vivo, these endogenous self peptides are not naturally presented in sufficient density by somatic cells expressing MHC class I molecules. They can, however, be presented if added exogenously. Thus, our data imply that CTLs are only tolerant of those endogenous self peptide sequences that are presented by MHC class I-positive cells in a physiological manner.     

Murine MHC polymorphism and T cell specificities

The major histocompatibility complex (MHC) genes are polymorphic in mouse and man. The products of these genes are receptors for peptides, which while bound, are displayed to T lymphocytes. When bound peptides from antigens are recognized by T lymphocytes, an immune response is initiated against the antigens. This study assessed the relation of the polymorphic MHC molecules to their peptide specificity. The results indicate that although an individual of the species has a limited ability to recognize antigens, the species as a whole has broad reactivity. This rationalizes the extreme polymorphism observed.     

Altered nociceptive neuronal circuits after neonatal peripheral inflammation

Nociceptive neuronal circuits are formed during embryonic and postnatal times when painful stimuli are normally absent or limited. Today, medical procedures for neonates with health risks can involve tissue injury and pain for which the long-term effects are unknown. To investigate the impact of neonatal tissue injury and pain on development of nociceptive neuronal circuitry, we used an animal model of persistent hind paw peripheral inflammation. We found that, as adults, these animals exhibited spinal neuronal circuits with increased input and segmental changes in nociceptive primary afferent axons and altered responses to sensory stimulation.     

Neuroscience. More to seeing than meets the eye

A single event may elicit several different sensory stimuli such as vision, sound, and touch. But how does the brain know which of the many different stimuli arriving in the sensory cortex of the brain are connected? In her Perspective, de Gelder discusses new findings showing that when a touch is applied on the same side of the body as a visual cue, vision is enhanced (Macaluso et al.). She explains that this effect is due to neurons projecting from the somatosensory (touch) area of the sensory cortex back to the visual cortex. These neurons keep the visual cortex informed about tactile stimuli elicited at the same time as the visual stimuli.     

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.     

A neural mechanism for working and recognition memory in inferior temporal cortex

Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurrently viewing other items. The neuronal response to an incoming visual stimulus was attenuated if it matched a stimulus actively held in working memory, even when several other stimuli intervened. The neuronal response to novel stimuli declined as the stimuli became familiar to the animal. IT neurons appear to function as adaptive mnemonic "filters" that preferentially pass information about new, unexpected, or not recently seen stimuli.     

Regulation of CD8+ T cell development by thymus-specific proteasomes

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.     

Glia are essential for sensory organ function in C. elegans

Sensory organs are composed of neurons, which convert environmental stimuli to electrical signals, and glia-like cells, whose functions are not well understood. To decipher glial roles in sensory organs, we ablated the sheath glial cell of the major sensory organ of Caenorhabditis elegans. We found that glia-ablated animals exhibit profound sensory deficits and that glia provide activities that affect neuronal morphology, behavior generation, and neuronal uptake of lipophilic dyes. To understand the molecular bases of these activities, we identified 298 genes whose messenger RNAs are glia-enriched. One gene, fig-1, encodes a labile protein with conserved thrombospondin TSP1 domains. FIG-1 protein functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. Our results suggest that glia are required for multiple aspects of sensory organ function.     

Transport of peptide-MHC class II complexes in developing dendritic cells

Major histocompatibility complex class II (MHC II) molecules capture peptides within the endocytic pathway to generate T cell receptor (TCR) ligands. Immature dendritic cells (DCs) sequester intact antigens in lysosomes, processing and converting antigens into peptide-MHC II complexes upon induction of DC maturation. The complexes then accumulate in distinctive, nonlysosomal MHC II+ vesicles that appear to migrate to the cell surface. Although the vesicles exclude soluble lysosomal contents and antigen-processing machinery, many contain MHC I and B7 costimulatory molecules. After arrival at the cell surface, the MHC and costimulatory molecules remain clustered. Thus, transport of peptide-MHC II complexes by DCs not only accomplishes transfer from late endocytic compartments to the plasma membrane, but does so in a manner that selectively concentrates TCR ligands and costimulatory molecules for T cell contact.     

中国林蛙嗅觉系统和犁鼻系统的显微结构

为了探讨两栖动物嗅器和犁鼻器在种系发生中的意义,用光学显微镜观察了中国林蛙嗅觉系统和犁鼻系统的组织结构。结果显示,嗅器可分为主嗅室、中室和下室3部分;主嗅室被覆嗅上皮,中室和下室被覆非嗅上皮。犁鼻腔位于嗅器的腹内侧,与下室相通,被覆发达的犁鼻上皮。背侧嗅神经起始于主嗅室背侧嗅上皮,经由嗅球腹外侧和前部进入同侧嗅球;犁鼻神经起始于犁鼻器上皮,经由嗅球腹正中部进入同侧副嗅球。     

甘肃鼢鼠与根田鼠的犁鼻器和副嗅球结构研究

为了探讨地下鼠犁鼻系统与地面鼠的差异及其与地面鼠嗅觉功能相适应的特点,用组织学方法对甘肃鼢鼠(Myospalax cansus)与根田鼠(Microtus oeconomus)的副嗅球和犁鼻器结构并进行了差异性研究。结果表明,2种鼠的犁鼻器均位于鼻腔前端鼻中隔基部两侧,呈管状;甘肃鼢鼠犁鼻上皮厚度、副嗅球颗粒细胞和僧帽细胞带宽比根田鼠发达;甘肃鼢鼠犁鼻器、副嗅球的性二型分化比根田鼠显著。2种鼠各自犁鼻器和副嗅球的形态有一定的对应关系,甘肃鼢鼠犁鼻上皮、副嗅球厚而短;根田鼠犁鼻上皮、副嗅球薄而长。这种对应关系可能与犁鼻器和副嗅球之间存在着神经投射有关。     

NompC TRP channel required for vertebrate sensory hair cell mechanotransduction

The senses of hearing and balance in vertebrates rely on the sensory hair cells (HCs) of the inner ear. The central element of the HC's transduction apparatus is a mechanically gated ion channel of unknown identity. Here we report that the zebrafish ortholog of Drosophila no mechanoreceptor potential C (nompC), which encodes a transient receptor potential (TRP) channel, is critical for HC mechanotransduction. In zebrafish larvae, nompC is selectively expressed in sensory HCs. Morpholino-mediated removal of nompC function eliminated transduction-dependent endocytosis and electrical responses in HCs, resulting in larval deafness and imbalance. These observations indicate that nompC encodes a vertebrate HC mechanotransduction channel.     

Contributions of bird studies to biology

Birds are widely distributed, highly diversified, and exhibit behavior and social organizations equal in complexity to mammals, yet they are generally more conspicuous and approachable in natural environments. These attributes make birds excellent subjects in many areas of biological research. The topics in which studies on birds have figured prominently include the mechanisms of species formation, the regulation of the distribution and abundance of animals, the effects of the environment on behavior and physiology, the biological and evolutionary significance of variations in social organizations, the encoding of information in animal communication, the sensory basis for migration and navigation, the effects of hormones on nerve cells and behavior, the ontogeny of brain and behavior, and the structure and function of the vertebrate brain. The outstanding record of avian research suggests that birds will continue to provide important models for developing and testing new ideas in various fields of biology.