Diverse dynamics of glutamatergic input from sensory neurons underlie heterogeneous responses of olfactory bulb outputs in vivo

Mapping Intimacies ◽

10.1101/692574 ◽

2019 ◽

Cited By ~ 1

Author(s):

Andrew K. Moran ◽

Thomas P. Eiting ◽

Matt Wachowiak

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Sensory Input ◽

Primary Source ◽

Glutamate Signaling ◽

Simultaneous Imaging ◽

Cell Responses ◽

Highly Correlated

ABSTRACTMitral/tufted (MT) cells of the olfactory bulb (OB) show diverse temporal responses to odorant stimulation that are thought to encode odor information. To understand the role of sensory input dynamics versus OB circuit mechanisms in generating this diversity, we imaged glutamate signaling onto MT cell dendrites in anesthetized and awake mice. We found surprising diversity in the dynamics of these signals, including excitatory, suppressive, and biphasic responses as well as nonlinear changes in glutamate signaling across inhalations. Simultaneous imaging of glutamate and calcium signals from MT cell dendrites revealed highly correlated responses for both signals. Glutamate responses were only weakly impacted by blockade of postsynaptic activity, implicating sensory neurons as a primary source of glutamate signaling onto MT cells. Thus, the dynamics of sensory input alone, rather than emergent features of OB circuits, may account for much of the diversity in MT cell responses that underlies OB odor representations.

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Immature olfactory sensory neurons provide behaviorally useful sensory input to the olfactory bulb

10.1101/2021.01.06.425578 ◽

2021 ◽

Author(s):

Jane S Huang ◽

Tenzin Kunkhyen ◽

Beichen Liu ◽

Ryan J Muggleton ◽

Jonathan T Avon ◽

...

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Sensory Input ◽

Odorant Receptors ◽

Projection Neurons ◽

Olfactory Sensory Neurons ◽

Odor Processing ◽

Newborn Neurons ◽

Behavioral Assays

Postnatal neurogenesis provides an opportunity to understand how newborn neurons functionally integrate into circuits to restore lost function. Newborn olfactory sensory neurons (OSNs) wire into highly organized olfactory bulb (OB) circuits throughout life, enabling lifelong plasticity and regeneration. Immature OSNs can form functional synapses capable of evoking firing in OB projection neurons. However, what contribution, if any, immature OSNs make to odor processing is unknown. Indeed, because immature OSNs can express multiple odorant receptors, any input that they do provide could degrade the odorant selectivity of input to OB glomeruli. Here, we used a combination of in vivo 2-photon calcium imaging, optogenetics, electrophysiology and behavioral assays to show that immature OSNs provide odor input to the OB, where they form monosynaptic connections with excitatory neurons. Importantly, immature OSNs responded as selectively to odorants as mature OSNs. Furthermore, mice successfully performed odor detection tasks using sensory input from immature OSNs alone. Immature OSNs responded more strongly to low odorant concentrations but their responses were less concentration dependent than those of mature OSNs, suggesting that immature and mature OSNs provide distinct odor input streams to each glomerulus. Together, our findings suggest that sensory input mediated by immature OSNs plays a previously unappreciated role in olfactory-guided behavior.

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PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

Cell Death and Disease ◽

10.1038/s41419-021-04013-y ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Dawei Chen ◽

Zhenguo Zhao ◽

Lu Chen ◽

Qinghua Li ◽

Jixue Zou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Alternative Splicing ◽

Protein Function ◽

Vital Role ◽

Normal Tissues ◽

Mechanistic Analysis ◽

Highly Correlated ◽

Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

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Role of prostaglandin E2 in the synthesis of the pro-inflammatory cytokine interleukin-6 in primary sensory neurons: an in vivo and in vitro study

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2011.07230.x ◽

2011 ◽

Vol 118 (5) ◽

pp. 841-854 ◽

Cited By ~ 38

Author(s):

Bruno St-Jacques ◽

Weiya Ma

Keyword(s):

Prostaglandin E2 ◽

Sensory Neurons ◽

Interleukin 6 ◽

Inflammatory Cytokine ◽

In Vitro Study ◽

Vitro Study ◽

Primary Sensory Neurons

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Sensory Transmission is Bi-directionally Modulated by Astrocytic Ca2+ in Barrel Cortex of Behaving Mice

10.21203/rs.3.rs-199750/v1 ◽

2021 ◽

Author(s):

Simeng Gu ◽

Wei Wang ◽

Kuan Zhang ◽

Rou Feng ◽

Naling Li ◽

...

Keyword(s):

Sensory Input ◽

Barrel Cortex ◽

Synaptic Function ◽

Metabolic Clearance ◽

Sleep State ◽

Two Photon Microscopy ◽

Two Photon ◽

Sensory Transmission

Abstract Different effects of astrocyte during sleep and awake have been extensively studied, especially for metabolic clearance by the glymphatic system, which works during sleep and stops working during waking states. However, how astrocytes contribute to modulation of sensory transmission during sleep and awake animals remain largely unknown. Recent advances in genetically encoded Ca2+ indicators have provided a wealth of information on astrocytic Ca2+, especially in their fine perisynaptic processes, where astrocytic Ca2+ most likely affects the synaptic function. Here we use two-photon microscopy to image astrocytic Ca2+ signaling in freely moving mice trained to run on a wheel in combination with in vivo whole-cell recordings to evaluate the role of astrocytic Ca2+ signaling in different behavior states. We found that there are two kinds of astrocytic Ca2+ signaling: a small long-lasting Ca2+ increase during sleep state and a sharp widespread but short-long-lasting Ca2+ spike when the animal was awake (fluorescence increases were 23.2 ± 14.4% for whisker stimulation at sleep state, compared with 73.3 ± 11.7% for at awake state, paired t-test, p < 0.01). The small Ca2+ transients decreased extracellular K+, hyperpolarized the neurons, and suppressed sensory transmission; while the large Ca2+ wave enhanced sensory input, contributing to reliable sensory transmission in aroused states. Locus coeruleus activation works as a switch between these two kinds of astrocytic Ca2+ elevation. Thus, we show that cortical astrocytes play an important role in processing of sensory input. These two types of events appear to have different pharmacological sources and may play a different role in facilitating the efficacy of sensory transmission.

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Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations

International Immunology ◽

10.1093/intimm/13.12.1583 ◽

2001 ◽

Vol 13 (12) ◽

pp. 1583-1593 ◽

Cited By ~ 113

Author(s):

Amariliz Rivera ◽

Chiann-Chyi Chen ◽

Naomi Ron ◽

Joseph P. Dougherty ◽

Yacov Ron

Keyword(s):

T Cell ◽

B Cells ◽

Lymph Nodes ◽

Cell Expansion ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cell Responses ◽

Antigen Presenting

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Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

eLife ◽

10.7554/elife.16335 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 24

Author(s):

Benjamin Roland ◽

Rebecca Jordan ◽

Dara L Sosulski ◽

Assunta Diodato ◽

Izumi Fukunaga ◽

...

Keyword(s):

Olfactory Bulb ◽

Transgenic Mice ◽

Neural Correlates ◽

Mitral Cell ◽

Inhibitory Circuits ◽

Cell Responses ◽

Mechanistic Basis ◽

Signal Normalization ◽

Whole Cell Recordings

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a “monoclonal nose”, glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a “monoclonal nose” and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output.

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Role of Axonal Odorant Receptors in Olfactory Topography

Neuroscience Insights ◽

10.1177/2633105520923411 ◽

2020 ◽

Vol 15 ◽

pp. 263310552092341

Author(s):

Claudia Lodovichi

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Axon Terminal ◽

Internal Representation ◽

Dual Role ◽

Odorant Receptors ◽

Topographic Map ◽

And Function ◽

Guidance Molecule

A unique feature in the organization of the olfactory system is the dual role of the odorant receptors: they detect odors in the nasal epithelium and they play an instructive role in the convergence of olfactory sensory neuron axons in specific loci, ie, glomeruli, in the olfactory bulb. The dual role is corroborated by the expression of the odorant receptors in 2 specific locations of the olfactory sensory neurons: the cilia that protrude in the nostril, where the odorant receptors interact with odors, and the axon terminal, a suitable location for a potential axon guidance molecule. The mechanism of activation and function of the odorant receptors expressed at the axon terminal remained unknown for almost 20 years. A recent study identified the first putative ligand of the axonal odorant receptors, phosphatidylethanolamine-binding protein1, a molecule expressed in the olfactory bulb. The distinctive mechanisms of activation of the odorant receptors expressed at the opposite locations in sensory neurons, by odors, at the cilia, and by molecules expressed in the olfactory bulb, at the axon terminal, explain the dual role of the odorant receptors and link the specificity of odor perception with its internal representation, in the topographic map.

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Thallium-201 Imaging in Intact Olfactory Sensory Neurons with Reduced Pre-Synaptic Inhibition In Vivo

Molecular Neurobiology ◽

10.1007/s12035-020-02078-y ◽

2020 ◽

Vol 57 (12) ◽

pp. 4989-4999

Author(s):

Hideaki Shiga ◽

Hiroshi Wakabayashi ◽

Kohshin Washiyama ◽

Tomohiro Noguchi ◽

Tomo Hiromasa ◽

...

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Action Potentials ◽

Migration Rate ◽

Intranasal Administration ◽

Thallium 201 ◽

Nasal Administration ◽

Olfactory Sensory Neurons ◽

Synaptic Inhibition

Abstract In this study, we determined whether the 201Tl (thallium-201)-based olfactory imaging is affected if olfactory sensory neurons received reduced pre-synaptic inhibition signals from dopaminergic interneurons in the olfactory bulb in vivo. The thallium-201 migration rate to the olfactory bulb and the number of action potentials of olfactory sensory neurons were assessed 3 h following left side nasal administration of rotenone, a mitochondrial respiratory chain complex I inhibitor that decreases the number of dopaminergic interneurons without damaging the olfactory sensory neurons in the olfactory bulb, in mice (6–7 animals per group). The migration rate of thallium-201 to the olfactory bulb was significantly increased following intranasal administration of thallium-201 and rotenone (10 μg rotenone, p = 0.0012; 20 μg rotenone, p = 0.0012), compared with that in control mice. The number of action potentials was significantly reduced in the olfactory sensory neurons in the rotenone treated side of 20 μg rotenone-treated mice, compared with that in control mice (p = 0.0029). The migration rate of thallium-201 to the olfactory bulb assessed with SPECT-CT was significantly increased in rats 24 h after the left intranasal administration of thallium-201 and 100 μg rotenone, compared with that in control rats (p = 0.008, 5 rats per group). Our results suggest that thallium-201 migration to the olfactory bulb is increased in intact olfactory sensory neurons with reduced pre-synaptic inhibition from dopaminergic interneurons in olfactory bulb glomeruli.

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T cell-intrinsic role of IL-6 signaling in primary and memory responses

eLife ◽

10.7554/elife.01949 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 73

Author(s):

Simone A Nish ◽

Dominik Schenten ◽

F Thomas Wunderlich ◽

Scott D Pope ◽

Yan Gao ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Suppressive Effect ◽

Immune Recognition ◽

Th17 Response ◽

Cell Responses ◽

Underlying Mechanisms ◽

Specific Deletion

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1β to block the suppressive effect of Tregs on CD4+ T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Rα-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4+ T cell memory formation.

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