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1.
Environmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These "thermoTRPs" are activated at distinct temperature thresholds and are typically expressed in sensory neurons. TRPV3 is activated by heat (>33 degrees C) and, unlike most thermoTRPs, is expressed in mouse keratinocytes. We found that TRPV3 null mice have strong deficits in responses to innocuous and noxious heat but not in other sensory modalities; hence, TRPV3 has a specific role in thermosensation. The natural compound camphor, which modulates sensations of warmth in humans, proved to be a specific activator of TRPV3. Camphor activated cultured primary keratinocytes but not sensory neurons, and this activity was abolished in TRPV3 null mice. Therefore, heat-activated receptors in keratinocytes are important for mammalian thermosensation.  相似文献   

2.
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.  相似文献   

3.
The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.  相似文献   

4.
为从细胞水平上研究独角雪冰鱼Chionodraco hamatus和伯氏肩孔南极鱼Trematomus bernacchii的低温适应能力,采用RT-PCR方法,获得独角雪冰鱼和伯氏肩孔南极鱼的瞬时受体电位阳离子通道蛋白(transient receptor potential channels V1,TRPV1)基因序列,其开放阅读框全长均为2310 bp;生物信息学分析表明,两种南极鱼TRPV1基因均编码769氨基酸残基,预测其蛋白相对分子质量分别为88 210和88 160,理论等电点分别为7.63和8.26;两种南极鱼TRPV1蛋白均无信号肽;亚细胞定位显示,TRPV1蛋白主要在细胞膜和内质网中发挥生物学功能;理化性质分析表明,两种南极鱼的TRPV1为不溶性跨膜蛋白,分别有34、35个磷酸化位点和6、5个糖基化位点,二者均含有6个跨膜结构域、5个锚蛋白结构域,二级结构以随机卷曲为主;同源性分析显示,独角雪冰鱼TRPV1氨基酸序列与伯氏肩孔南极鱼的一致性最高,为93.4%,与其他物种的一致性为44.3%~69.8%;低温适应试验结果显示,两种南极鱼的TRPV1基因不能被温度所激活。研究表明,独角雪冰鱼和伯氏肩孔南极鱼TRPV1基因可能与低温适应无关。  相似文献   

5.
Insects are poikilothermic animals, and temperature is one of the most important abiotic factors affecting their spread and distribution. For example, differences in thermal tolerance may underlie the significant differences in geographical distributions between the native AsiaII3 and invasive MED (Mediterranean) cryptic Bemisia tabaci species in China. Transient receptor potential (TRP) channels are key components of the insect temperature perception system and act as molecular thermometers since they can be activated by specific changes in temperature. In this study, we cloned and characterized the AsiaII3 BtTRP gene and revealed its functions in the response to thermal stress. The full-length cDNA of BtTRP was 3821 bp, with a 3501-bp open reading frame encoding a 132.05-kDa protein. Comparing the deduced amino acid sequences of AsiaII3 BtTRP and MED TRP revealed five amino acid differences. In situ hybridization indicated that BtTRP might be widely expressed throughout the AsiaII3 adult body. BtTRP mRNA expression reached the highest levels after exposure to mild thermal stimuli (12 and 35°C), showing that BtTRP expression can be induced by temperature stress. Furthermore, the thermal tolerance of AsiaII3 after BtTRP dsRNA feeding was significantly lower than that of the control. Taken together, the present study highlights the importance of TRP channels for B. tabaci thermal resistance, and allows us to infer that the differences in amino acids between AsiaII3 and MED might cause the differences in thermal tolerance of these two cryptic species. This study provides a new direction for investigating geographic distribution differences between invasive and native insects.  相似文献   

6.
Aphelinus asychis is an important aphid endoparasitoid. Under field and greenhouse conditions, high temperature is one of the factors limiting the application of A. asychis for biological pest control. To explore the potential role of transient receptor potential(TRP) channels and heat shock proteins(HSPs) in this process, we identified 11 genes encoding TRP channels and nine genes encoding HSPs. Three proteins(AasyTRPA5, AasyPyrexia, AasyPainless) that belong to transient receptor potential ankyrin(TRPA) subfamily and nine HSPs are involved in the response to high temperature. We also investigated the survival of A. asychis and the response of the identified TRP channels and HSPs to high temperature. The results showed that the maximum temperature that allowed A. asychis survival was approximately 41℃; females had higher survival rates than that of the males at 40 and 41℃. Short-term heat-shock resulted in increased expression of Aasyshsp in males, and Aasyhsp40, Aasyhsp68, Aasyhsp70-4, Aasyhsp70-5 and Aasyhsp90 were upregulated and then downregulated, whereas Aasyhsp70-3 was upregulated at 41℃. Moreover, Aasyhsp40 and Aasyhsp90 showed higher expression levels in females, while Aasyshsp and Aasyhsp70-3 presented opposite expression patterns. At temperature above 35℃, expression of AasyPyrexia in females was significant higher than that in males, whereas AasyPainless and AasyTRPA5 presented higher expression in males at 40 and 41℃, respectively. Altogether, these results indicate that protection against thermal stress in A. asychis is coordinated by TRP channels and HSPs. These findings provide a basis for understanding the potential mechanism of A. asychis in response to high temperatures.  相似文献   

7.
We investigated the effect of activating a competing, artificially generated, neural representation on encoding of contextual fear memory in mice. We used a c-fos-based transgenic approach to introduce the hM(3)D(q) DREADD receptor (designer receptor exclusively activated by designer drug) into neurons naturally activated by sensory experience. Neural activity could then be specifically and inducibly increased in the hM(3)D(q)-expressing neurons by an exogenous ligand. When an ensemble of neurons for one context (ctxA) was artificially activated during conditioning in a distinct second context (ctxB), mice formed a hybrid memory representation. Reactivation of the artificially stimulated network within the conditioning context was required for retrieval of the memory, and the memory was specific for the spatial pattern of neurons artificially activated during learning. Similar stimulation impaired recall when not part of the initial conditioning.  相似文献   

8.
The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.  相似文献   

9.
Of 76 cutaneously activated neurons recorded from the ventral posterior thalamus of awake, behaving monkeys, nine were weakly excited by innocuous skin stimulation and responded maximally only when noxious mechanical cutaneous stimuli were delivered within small, contralateral receptive fields. These results show that neurons capable of encoding the spatial and temporal features of noxious stimuli are located in the ventral posterior thalamus of the awake primate.  相似文献   

10.
Neurotrophins regulate survival, axonal growth, and target innervation of sensory and other neurons. Neurotrophin-3 (NT-3) is expressed specifically in cells adjacent to extending axons of dorsal root ganglia neurons, and its absence results in loss of most of these neurons before their axons reach their targets. However, axons are not required for NT-3 expression in limbs; instead, local signals from ectoderm induce NT-3 expression in adjacent mesenchyme. Wnt factors expressed in limb ectoderm induce NT-3 in the underlying mesenchyme. Thus, epithelial-mesenchymal interactions mediated by Wnt factors control NT-3 expression and may regulate axonal growth and guidance.  相似文献   

11.
In crowded visual scenes, attention is needed to select relevant stimuli. To study the underlying mechanisms, we recorded neurons in cortical area V4 while macaque monkeys attended to behaviorally relevant stimuli and ignored distracters. Neurons activated by the attended stimulus showed increased gamma-frequency (35 to 90 hertz) synchronization but reduced low-frequency (<17 hertz) synchronization compared with neurons at nearby V4 sites activated by distracters. Because postsynaptic integration times are short, these localized changes in synchronization may serve to amplify behaviorally relevant signals in the cortex.  相似文献   

12.
Initiation and performance of the swimming movement in the leech (Hirudo medicinalis) are controlled by neurons organized at at least four functional levels-sensory neurons, gating neurons, oscillator neurons, and motor neurons. A paired neuron, designated as Trl, in the subesophageal ganglion of the leech has now been shown to define a fifth level, interposed between sensory and gating neurons. Cell Trl is activated by pressure and nociceptive mechanosensory neurons, which mediate bodywall stimulus-evoked swimming activity in intact leeches. In the isolated leech nervous system, brief stimulation of cell Trl elicits sustained activation of the gating neurons and triggers the onset of swimmning activity. The synaptic interactions between all five levels of control are direct. Discovery of the Trl cells thus completes the identification of a synaptic pathway by which mechanosensory stimulation leads to the swimming movements of the leech.  相似文献   

13.
Expression of c-fos protein in brain: metabolic mapping at the cellular level   总被引：61，自引：0，他引：61  
The proto-oncogene c-fos is expressed in neurons in response to direct stimulation by growth factors and neurotransmitters. In order to determine whether the c-fos protein (Fos) and Fos-related proteins can be induced in response to polysynaptic activation, rat hindlimb motor/sensory cortex was stimulated electrically and Fos expression examined immunohistochemically. Three hours after the onset of stimulation, focal nuclear Fos staining was seen in motor and sensory thalamus, pontine nuclei, globus pallidus, and cerebellum. Moreover, 24-hour water deprivation resulted in Fos expression in paraventricular and supraoptic nuclei. Fos immunohistochemistry therefore provides a cellular method to label polysynaptically activated neurons and thereby map functional pathways.  相似文献   

14.
Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a class I MHC receptor component, CD3zeta, refinement of connections between retina and central targets during development is incomplete. In the hippocampus of adult mutants, N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) is enhanced, and long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by distinct mosaics of neurons, reflecting a potential for diverse neuronal functions. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS).  相似文献   

15.
Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.  相似文献   

16.
Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca(2+)) signals ("sparklets") in the vascular endothelium of resistance arteries that represent Ca(2+) influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca(2+)-sensitive potassium (K(+)) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca(2+) influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca(2+) sensitivity of IK and SK channels to cause vasodilation.  相似文献   

17.
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.  相似文献   

18.
Carbon dioxide (CO2) is an important environmental cue for many organisms but is odorless to humans. It remains unclear whether the mammalian olfactory system can detect CO2 at concentrations around the average atmospheric level (0.038%). We demonstrated the expression of carbonic anhydrase type II (CAII), an enzyme that catabolizes CO2, in a subset of mouse olfactory neurons that express guanylyl cyclase D (GC-D+ neurons) and project axons to necklace glomeruli in the olfactory bulb. Exposure to CO2 activated these GC-D+ neurons, and exposure of a mouse to CO2 activated bulbar neurons associated with necklace glomeruli. Behavioral tests revealed CO2 detection thresholds of approximately 0.066%, and this sensitive CO2 detection required CAII activity. We conclude that mice detect CO2 at near-atmospheric concentrations through the olfactory subsystem of GC-D+ neurons.  相似文献   

19.
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.  相似文献   

20.
OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.  相似文献   

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