scholarly journals Bacteria-derived peptidoglycan triggers an NF-kB dependent response in Drosophila gustatory neurons

2021 ◽  
Author(s):  
Ambra Masuzzo ◽  
Gerard Maniere ◽  
Yael Grosjean Grosjean ◽  
Leopold Kurz ◽  
Julien Royet

Probing the external world is essential for eukaryotes to distinguish beneficial from pathogenic microorganisms. If it is clear that this task falls to the immune cells, recent work shows that neurons can also detect microbes, although the molecules and mechanisms involved are less characterized. In Drosophila, detection of bacteria-derived peptidoglycan by pattern recognition receptor (PRR) of the PGRP family expressed in immune cells, triggers NF-kB/IMD dependent signaling. We show here that one PGRP protein, called PGRP-LB, is expressed in some proboscis's bitter taste neurons. In vivo calcium imaging reveals that the PGRP/IMD pathway is cell-autonomously required in these neurons to transduce the PGN signal. We finally show that NF-kB/IMD pathway activation in bitter neurons influences fly behavior. This demonstrates that flies use the same bacterial elicitor and signaling module to sense bacterial presence via the peripheral nervous system and trigger an anti-bacterial response in immune-competent cells.

2018 ◽  
Author(s):  
Gal Mishne ◽  
Ronald R. Coifman ◽  
Maria Lavzin ◽  
Jackie Schiller

AbstractRecent advances in experimental methods in neuroscience enable measuring in-vivo activity of large populations of neurons at cellular level resolution. To leverage the full potential of these complex datasets and analyze the dynamics of individual neurons, it is essential to extract high-resolution regions of interest, while addressing demixing of overlapping spatial components and denoising of the temporal signal of each neuron. In this paper, we propose a data-driven solution to these challenges, by representing the spatiotemporal volume as a graph in the image plane. Based on the spectral embedding of this graph calculated across trials, we propose a new clustering method, Local Selective Spectral Clustering, capable of handling overlapping clusters and disregarding clutter. We also present a new nonlinear mapping which recovers the structural map of the neurons and dendrites, and global video denoising. We demonstrate our approach on in-vivo calcium imaging of neurons and apical dendrites, automatically extracting complex structures in the image domain, and denoising and demixing their time-traces.


2018 ◽  
Vol 84 (1) ◽  
pp. e51 ◽  
Author(s):  
Alexander D. Jacob ◽  
Adam I. Ramsaran ◽  
Andrew J. Mocle ◽  
Lina M. Tran ◽  
Chen Yan ◽  
...  

2022 ◽  
Vol 225 (1) ◽  
Author(s):  
Madeleine S. Junkins ◽  
Sviatoslav N. Bagriantsev ◽  
Elena O. Gracheva

ABSTRACT Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the physiological changes that occur during hibernation have been comprehensively researched, the role of the nervous system in this process remains relatively underexplored. In this Review, we adopt the perspective that the nervous system plays an active, essential role in facilitating and supporting hibernation. Accumulating evidence strongly suggests that the hypothalamus enters a quiescent state in which powerful drives to thermoregulate, eat and drink are suppressed. Similarly, cardiovascular and pulmonary reflexes originating in the brainstem are altered to permit the profoundly slow heart and breathing rates observed during torpor. The mechanisms underlying these changes to the hypothalamus and brainstem are not currently known, but several neuromodulatory systems have been implicated in the induction and maintenance of hibernation. The intersection of these findings with modern neuroscience approaches, such as optogenetics and in vivo calcium imaging, has opened several exciting avenues for hibernation research.


2019 ◽  
Vol 11 (522) ◽  
pp. eaaw6435 ◽  
Author(s):  
Boris D. Heifets ◽  
Juliana S. Salgado ◽  
Madison D. Taylor ◽  
Paul Hoerbelt ◽  
Daniel F. Cardozo Pinto ◽  
...  

The extensively abused recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA) has shown promise as an adjunct to psychotherapy for treatment-resistant psychiatric disease. It is unknown, however, whether the mechanisms underlying its prosocial therapeutic effects and abuse potential are distinct. We modeled both the prosocial and nonsocial drug reward of MDMA in mice and investigated the mechanism of these processes using brain region–specific pharmacology, transgenic manipulations, electrophysiology, and in vivo calcium imaging. We demonstrate in mice that MDMA acting at the serotonin transporter within the nucleus accumbens is necessary and sufficient for MDMA’s prosocial effect. MDMA’s acute rewarding properties, in contrast, require dopaminergic signaling. MDMA’s prosocial effect requires 5-HT1b receptor activation and is mimicked by d-fenfluramine, a selective serotonin-releasing compound. By dissociating the mechanisms of MDMA’s prosocial effects from its addictive properties, we provide evidence for a conserved neuronal pathway, which can be leveraged to develop novel therapeutics with limited abuse liability.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A2-A2
Author(s):  
C E Mahoney ◽  
W Zhao ◽  
A Coffey ◽  
C Woods ◽  
D Kroeger ◽  
...  

Abstract Introduction People with narcolepsy type 1 report that cataplexy is triggered most often by positive social experiences such as laughing with friends, yet the mechanisms through which social interaction promotes cataplexy are unknown. We hypothesize a subpopulation of central amygdala neurons that are sensitive to the prosocial neuropeptide, oxytocin (CeAOTR), respond to positive valence and trigger cataplexy. Methods We have used in vivo calcium imaging, chemogenetic and optogenetic approaches to characterize the activity pattern of these neurons and to manipulate their activity state. Results Cre-dependent anterograde tracing of the CeAOTR neurons of the central amygdala indicate a moderate to dense projection to the REM sleep-regulatory region of the ventral lateral periaqueductal gray (vlPAG). Additionally, Channel Rhodopsin Assisted Circuit Mapping (CRACM) experiments show that CeAOTR neurons inhibit vlPAG neurons that innervate the REM atonia-promoting region, the sublaterodorsal nucleus. Targeted photostimulation (15Hz (10ms) for 20sec every hour) of the CeAOTR fibers in the vlPAG doubled the amount of cataplexy. Preliminary in vivo calcium imaging indicates that the CeAOTR are active just prior to the onset of cataplexy. Chemogenetic and optogenetic activation of CeAOTR neurons increased cataplexy. Conclusion We conclude that the CeAOTR subpopulation is sufficient to promote cataplexy. Our future directions include determining the necessity of these oxytocin sensitive neurons in cataplexy under different conditions of positive valence. Support R01 NS106032 and WakeUp Narcolepsy.


2015 ◽  
Vol 8 (1) ◽  
pp. 67-80 ◽  
Author(s):  
Denis Costechareyre ◽  
Florence Capo ◽  
Alexandre Fabre ◽  
Delphine Chaduli ◽  
Christine Kellenberger ◽  
...  

In Drosophila, peptidoglycan (PGN) is detected by PGN recognition proteins (PGRPs) that act as pattern recognition receptors. Some PGRPs such as PGRP-LB or PGRP-SCs are able to cleave PGN, therefore reducing the amount of immune elicitors and dampening immune deficiency (IMD) pathway activation. The precise role of PGRP-SC is less well defined because the PGRP-SC genes (PGRP-SC1a, PGRP-SC1b and PGRP-SC2) lie very close on the chromosome and have been studied using a deletion encompassing the three genes. By generating PGRP-SC-specific mutants, we reevaluated the roles of PGRP-LB, PGRP-SC1 and PGRP-SC2, respectively, during immune responses. We showed that these genes are expressed in different gut domains and that they follow distinct transcriptional regulation. Loss-of-function mutant analysis indicates that PGRP-LB is playing a major role in IMD pathway activation and bacterial load regulation in the gut, although PGRP-SCs are expressed at high levels in this organ. We also demonstrated that PGRP-SC2 is the main negative regulator of IMD pathway activation in the fat body. Accordingly, we showed that mutants for either PGRP-LB or PGRP-SC2 displayed a distinct susceptibility to bacteria depending on the infection route. Lastly, we demonstrated that PGRP-SC1 and PGRP-SC2 are required in vivo for full Toll pathway activation by Gram-positive bacteria.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Bocchio ◽  
Claire Gouny ◽  
David Angulo-Garcia ◽  
Tom Toulat ◽  
Thomas Tressard ◽  
...  

Abstract The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.


2011 ◽  
Vol 2011 (10) ◽  
pp. pdb.prot065805-pdb.prot065805
Author(s):  
B. Kuhn ◽  
T. M. Hoogland ◽  
S. S.- H. Wang

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