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Neurosensory perception of environmental cues modulates sperm motility critical for fertilization.
McKnight K, Hoang HD, Prasain JK, Brown N, Vibbert J, Hollister KA, Moore R, Ragains JR, Reese J, Miller MA
(2014) Science 344: 754-7
MeSH Terms: Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Environmental Exposure, Female, Fertilization, Male, Neurons, Afferent, Neurosecretory Systems, Oocytes, Ovum, Perception, Pheromones, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Sperm Motility, Spermatozoa, Transforming Growth Factor beta
Show Abstract · Added May 19, 2014
Environmental exposures affect gamete function and fertility, but the mechanisms are poorly understood. Here, we show that pheromones sensed by ciliated neurons in the Caenorhabditis elegans nose alter the lipid microenvironment within the oviduct, thereby affecting sperm motility. In favorable environments, pheromone-responsive sensory neurons secrete a transforming growth factor-β ligand called DAF-7, which acts as a neuroendocrine factor that stimulates prostaglandin-endoperoxide synthase [cyclooxygenase (Cox)]-independent prostaglandin synthesis in the ovary. Oocytes secrete F-class prostaglandins that guide sperm toward them. These prostaglandins are also synthesized in Cox knockout mice, raising the possibility that similar mechanisms exist in other animals. Our data indicate that environmental cues perceived by the female nervous system affect sperm function.
Copyright © 2014, American Association for the Advancement of Science.
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18 MeSH Terms
Impact of response duration on multisensory integration.
Ghose D, Barnett ZP, Wallace MT
(2012) J Neurophysiol 108: 2534-44
MeSH Terms: Acoustic Stimulation, Animals, Cats, Evoked Potentials, Auditory, Evoked Potentials, Visual, Neurons, Afferent, Photic Stimulation, Superior Colliculi, Time
Show Abstract · Added March 19, 2014
Multisensory neurons in the superior colliculus (SC) have been shown to have large receptive fields that are heterogeneous in nature. These neurons have the capacity to integrate their different sensory inputs, a process that has been shown to depend on the physical characteristics of the stimuli that are combined (i.e., spatial and temporal relationship and relative effectiveness). Recent work has highlighted the interdependence of these factors in driving multisensory integration, adding a layer of complexity to our understanding of multisensory processes. In the present study our goal was to add to this understanding by characterizing how stimulus location impacts the temporal dynamics of multisensory responses in cat SC neurons. The results illustrate that locations within the spatial receptive fields (SRFs) of these neurons can be divided into those showing short-duration responses and long-duration response profiles. Most importantly, discharge duration appears to be a good determinant of multisensory integration, such that short-duration responses are typically associated with a high magnitude of multisensory integration (i.e., superadditive responses) while long-duration responses are typically associated with low integrative capacity. These results further reinforce the complexity of the integrative features of SC neurons and show that the large SRFs of these neurons are characterized by vastly differing temporal dynamics, dynamics that strongly shape the integrative capacity of these neurons.
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9 MeSH Terms
The molecular and cellular basis of olfactory-driven behavior in Anopheles gambiae larvae.
Xia Y, Wang G, Buscariollo D, Pitts RJ, Wenger H, Zwiebel LJ
(2008) Proc Natl Acad Sci U S A 105: 6433-8
MeSH Terms: Animal Structures, Animals, Anopheles, Behavior, Animal, Gene Expression Regulation, Larva, Neurons, Afferent, Odorants, Olfactory Pathways, Organic Chemicals, Receptors, Odorant, Xenopus
Show Abstract · Added May 27, 2014
The mosquito Anopheles gambiae is the principal Afrotropical vector for human malaria. A central component of its vectorial capacity is the ability to maintain sufficient populations of adults. During both adult and preadult (larval) stages, the mosquitoes depend on the ability to recognize and respond to chemical cues that mediate feeding and survival. In this study, we used a behavioral assay to identify a range of odorant-specific responses of An. gambiae larvae that are dependent on the integrity of the larval antennae. Parallel molecular analyses have identified a subset of the An. gambiae odorant receptors (AgOrs) that are localized to discrete neurons within the larval antennae and facilitate odor-evoked responses in Xenopus oocytes that are consistent with the larval behavioral spectrum. These studies shed light on chemosensory-driven behaviors and represent molecular and cellular characterization of olfactory processes in mosquito larvae. These advances may ultimately enhance the development of vector control strategies, targeting olfactory pathways in larval-stage mosquitoes to reduce the catastrophic effects of malaria and other diseases.
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12 MeSH Terms
Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis.
Williams CL, Winkelbauer ME, Schafer JC, Michaud EJ, Yoder BK
(2008) Mol Biol Cell 19: 2154-68
MeSH Terms: Alleles, Animals, Body Patterning, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cilia, Coloring Agents, Conserved Sequence, Dendrites, Feeding Behavior, Genes, Helminth, Mutation, Neuroglia, Neurons, Afferent, Protein Transport, Transcription Factors
Show Abstract · Added January 20, 2015
Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.
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16 MeSH Terms
Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal medium spiny neurons.
Neely MD, Schmidt DE, Deutch AY
(2007) Neuroscience 149: 457-64
MeSH Terms: Animals, Cerebral Cortex, Chromatography, High Pressure Liquid, Coculture Techniques, Coloring Agents, Dendritic Spines, Denervation, Dopamine, Homovanillic Acid, Immunohistochemistry, Mesencephalon, Neostriatum, Neurons, Neurons, Afferent, Organ Culture Techniques, Propidium, Rats, Rats, Sprague-Dawley, Tyrosine 3-Monooxygenase
Show Abstract · Added May 27, 2014
The proximate cause of Parkinson's disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson's disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures composed of ventral mesencephalon, striatum, and cortex of the neonatal rat, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson's disease.
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19 MeSH Terms
Visual deprivation alters the development of cortical multisensory integration.
Carriere BN, Royal DW, Perrault TJ, Morrison SP, Vaughan JW, Stein BE, Wallace MT
(2007) J Neurophysiol 98: 2858-67
MeSH Terms: Action Potentials, Animals, Cats, Cerebral Cortex, Dose-Response Relationship, Radiation, Neurons, Afferent, Physical Stimulation, Reaction Time, Sensation, Sensory Deprivation
Show Abstract · Added March 19, 2014
It has recently been demonstrated that the maturation of normal multisensory circuits in the cortex of the cat takes place over an extended period of postnatal life. Such a finding suggests that the sensory experiences received during this time may play an important role in this developmental process. To test the necessity of sensory experience for normal cortical multisensory development, cats were raised in the absence of visual experience from birth until adulthood, effectively precluding all visual and visual-nonvisual multisensory experiences. As adults, semichronic single-unit recording experiments targeting the anterior ectosylvian sulcus (AES), a well-defined multisensory cortical area in the cat, were initiated and continued at weekly intervals in anesthetized animals. Despite having very little impact on the overall sensory representations in AES, dark-rearing had a substantial impact on the integrative capabilities of multisensory AES neurons. A significant increase was seen in the proportion of multisensory neurons that were modulated by, rather than driven by, a second sensory modality. More important, perhaps, there was a dramatic shift in the percentage of these modulated neurons in which the pairing of weakly effective and spatially and temporally coincident stimuli resulted in response depressions. In normally reared animals such combinations typically give rise to robust response enhancements. These results illustrate the important role sensory experience plays in shaping the development of mature multisensory cortical circuits and suggest that dark-rearing shifts the relative balance of excitation and inhibition in these circuits.
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10 MeSH Terms
Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system.
Von Stetina SE, Watson JD, Fox RM, Olszewski KL, Spencer WC, Roy PJ, Miller DM
(2007) Genome Biol 8: R135
MeSH Terms: Animals, Caenorhabditis elegans, Embryonic Development, Gene Expression, Gene Expression Profiling, Motor Neurons, Nervous System, Neurons, Afferent, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Synaptic Transmission
Show Abstract · Added February 3, 2014
BACKGROUND - With its fully sequenced genome and simple, well-defined nervous system, the nematode Caenorhabditis elegans offers a unique opportunity to correlate gene expression with neuronal differentiation. The lineal origin, cellular morphology and synaptic connectivity of each of the 302 neurons are known. In many instances, specific behaviors can be attributed to particular neurons or circuits. Here we describe microarray-based methods that monitor gene expression in C. elegans neurons and, thereby, link comprehensive profiles of neuronal transcription to key developmental and functional properties of the nervous system.
RESULTS - We employed complementary microarray-based strategies to profile gene expression in the embryonic and larval nervous systems. In the MAPCeL (Microarray Profiling C. elegans cells) method, we used fluorescence activated cell sorting (FACS) to isolate GFP-tagged embryonic neurons for microarray analysis. To profile the larval nervous system, we used the mRNA-tagging technique in which an epitope-labeled mRNA binding protein (FLAG-PAB-1) was transgenically expressed in neurons for immunoprecipitation of cell-specific transcripts. These combined approaches identified approximately 2,500 mRNAs that are highly enriched in either the embryonic or larval C. elegans nervous system. These data are validated in part by the detection of gene classes (for example, transcription factors, ion channels, synaptic vesicle components) with established roles in neuronal development or function. Of particular interest are 19 conserved transcripts of unknown function that are also expressed in the mammalian brain. In addition to utilizing these profiling approaches to define stage-specific gene expression, we also applied the mRNA-tagging method to fingerprint a specific neuron type, the A-class group of cholinergic motor neurons, during early larval development. A comparison of these data to a MAPCeL profile of embryonic A-class motor neurons identified genes with common functions in both types of A-class motor neurons as well as transcripts with roles specific to each motor neuron type.
CONCLUSION - We describe microarray-based strategies for generating expression profiles of embryonic and larval C. elegans neurons. These methods can be applied to particular neurons at specific developmental stages and, therefore, provide an unprecedented opportunity to obtain spatially and temporally defined snapshots of gene expression in a simple model nervous system.
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11 MeSH Terms
NKCC1 phosphorylation stimulates neurite growth of injured adult sensory neurons.
Pieraut S, Laurent-Matha V, Sar C, Hubert T, Méchaly I, Hilaire C, Mersel M, Delpire E, Valmier J, Scamps F
(2007) J Neurosci 27: 6751-9
MeSH Terms: Age Factors, Animals, Cells, Cultured, Humans, Intracellular Fluid, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurites, Neurons, Afferent, Phosphorylation, Sodium-Potassium-Chloride Symporters, Solute Carrier Family 12, Member 2
Show Abstract · Added August 13, 2010
Peripheral nerve section promotes regenerative, elongated neuritic growth of adult sensory neurons. Although the role of chloride homeostasis, through the regulation of ionotropic GABA receptors, in the growth status of immature neurons in the CNS begins to emerge, nothing is known of its role in the regenerative growth of injured adult neurons. To analyze the intracellular Cl- variation after a sciatic nerve section in vivo, gramicidin perforated-patch recordings were used to study muscimol-induced currents in mice dorsal root ganglion neurons isolated from control and axotomized neurons. We show that the reversal potential of muscimol-induced current, E(GABA-A), was shifted toward depolarized potentials in axotomized neurons. This was attributable to Cl- influx because removal of extracellular Cl- prevented this shift. Application of bumetanide, an inhibitor of NKCC1 cotransporter and E(GABA-A) recordings in sensory neurons from NKCC1-/- mice, identified NKCC1 as being responsible for the increase in intracellular Cl- in axotomized neurons. In addition, we demonstrate with a phospho-NKCC1 antibody that nerve injury induces an increase in the phosphorylated form of NKCC1 in dorsal root ganglia that could account for intracellular Cl- accumulation. Time-lapse recordings of the neuritic growth of axotomized neurons show a faster growth velocity compared with control. Bumetanide, the intrathecal injection of NKCC1 small interfering RNA, and the use of NKCC1-/- mice demonstrated that NKCC1 is involved in determining the velocity of elongated growth of axotomized neurons. Our results clearly show that NKCC1-induced increase in intracellular chloride concentration is a major event accompanying peripheral nerve regeneration.
1 Communities
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13 MeSH Terms
The C. elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception.
Winkelbauer ME, Schafer JC, Haycraft CJ, Swoboda P, Yoder BK
(2005) J Cell Sci 118: 5575-87
MeSH Terms: Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cilia, Gene Expression Regulation, Mutation, Neurons, Afferent, Time Factors, Transcription Factors
Show Abstract · Added January 20, 2015
Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal failure in children. Five nephrocystin (nephrocystin-1 to nephrocystin-5) genes, whose function is disrupted in NPH patients, have been identified and data indicate they form a complex at cell junctions and focal adhesions. More recently, the nephrocystin proteins have also been identified in cilia, as have multiple other cystic kidney disease related proteins. Significant insights into this cilia and cystic kidney disease connection have come from analyses in simpler eukaryotic organisms such as Caenorhabditis elegans. In this regard, we became interested in the C. elegans homologs of nephrocystin-1 (nph-1) and nephrocystin-4 (nph-4) from a database screen to identify genes coordinately regulated by the ciliogenic transcription factor DAF-19. Here we show that expression of nph-1 and nph-4 is DAF-19 dependent, that their expression is restricted to ciliated sensory neurons, and that both NPH-1 and NPH-4 concentrate at the transition zones at the base of the cilia, but are not found in the cilium axoneme. In addition, NPH-4 is required for the localization of NPH-1 to this domain. Interestingly, nph-1 or nph-4 mutants have no obvious cilia assembly defects; however, they do have abnormalities in cilia-mediated sensory functions as evidenced by abnormal chemotaxis and lifespan regulation. Our data suggest that rather than having a ciliogenic role, the NPH proteins play an important function as part of the sensory or signaling machinery of this organelle. These findings suggest that the defects in human NPH patients may not be the result of aberrant ciliogenesis but abnormal cilia-sensory functions.
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9 MeSH Terms
Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane.
Qin H, Burnette DT, Bae YK, Forscher P, Barr MM, Rosenbaum JL
(2005) Curr Biol 15: 1695-9
MeSH Terms: Animals, Biological Transport, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Membrane, Cilia, Green Fluorescent Proteins, Ion Channels, Membrane Proteins, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Afferent, TRPP Cation Channels, TRPV Cation Channels, Transient Receptor Potential Channels
Show Abstract · Added August 25, 2017
The membranes of all eukaryotic motile (9 + 2) and immotile primary (9 + 0) cilia harbor channels and receptors involved in sensory transduction (reviewed by). These membrane proteins are transported from the cytoplasm onto the ciliary membrane by vesicles targeted for exocytosis at a point adjacent to the ciliary basal body. Here, we use time-lapse fluorescence microscopy to demonstrate that select GFP-tagged sensory receptors undergo rapid vectorial transport along the entire length of the cilia of Caenorhabditis elegans sensory neurons. Transient receptor potential vanilloid (TRPV) channels OSM-9 and OCR-2 move in ciliary membranes at rates comparable to the intraflagellar transport (IFT) machinery located between the membrane and the underlying axonemal microtubules. OSM-9 motility is disrupted in certain IFT mutant backgrounds. Surprisingly, motility of transient receptor potential polycystin (TRPP) channel PKD-2 (polycystic kidney disease-2), a mechano-receptor, was not detected. Our study demonstrates that IFT, previously shown to be necessary for transport of axonemal components, is also involved in the motility of TRPV membrane protein movement along cilia of C. elegans sensory cells.
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15 MeSH Terms