Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish
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Born Granule Cells During Implicit Versus Explicit Olfactory Learning
RESEARCH ARTICLE Opposite regulation of inhibition by adult- born granule cells during implicit versus explicit olfactory learning Nathalie Mandairon1*, Nicola Kuczewski1, Florence Kermen1, Je´ re´ my Forest1, Maellie Midroit1, Marion Richard1, Marc Thevenet1, Joelle Sacquet1, Christiane Linster2,3, Anne Didier1 1Lyon Neuroscience Research Center, Neuroplasticity and Neuropathology of Olfactory Perception Team, CNRS UMR 5292, INSERM U1028, Universite´ de Lyon, Lyon, France; 2Computational Physiology Lab, Cornell University, Ithaca, United States; 3Department of Neurobiology and Behavior, Cornell University, Ithaca, United States Abstract Both passive exposure and active learning through reinforcement enhance fine sensory discrimination abilities. In the olfactory system, this enhancement is thought to occur partially through the integration of adult-born inhibitory interneurons resulting in a refinement of the representation of overlapping odorants. Here, we identify in mice a novel and unexpected dissociation between passive and active learning at the level of adult-born granule cells. Specifically, while both passive and active learning processes augment neurogenesis, adult-born cells differ in their morphology, functional coupling and thus their impact on olfactory bulb output. Morphological analysis, optogenetic stimulation of adult-born neurons and mitral cell recordings revealed that passive learning induces increased inhibitory action by adult-born neurons, probably resulting in more sparse and thus less overlapping odor representations. Conversely, after active learning inhibitory action is found to be diminished due to reduced connectivity. In this case, strengthened odor response might underlie enhanced discriminability. *For correspondence: DOI: https://doi.org/10.7554/eLife.34976.001 [email protected] Competing interests: The authors declare that no Introduction competing interests exist. Brain representations of the environment constantly evolve through learning mediated by different Funding: See page 13 plasticity mechanisms. -
Distinct Representations of Olfactory Information in Different Cortical Centres
LETTER doi:10.1038/nature09868 Distinct representations of olfactory information in different cortical centres Dara L. Sosulski1, Maria Lissitsyna Bloom1{, Tyler Cutforth1{, Richard Axel1 & Sandeep Robert Datta1{ Sensory information is transmitted to the brain where it must be behaviours, but is unlikely to specify innate behaviours. Rather, innate processed to translate stimulus features into appropriate beha- olfactory behaviours are likely to result from the activation of genetically vioural output. In the olfactory system, distributed neural activity determined, stereotyped neural circuits. We have therefore developed a in the nose is converted into a segregated map in the olfactory strategy to trace the projections from identified glomeruli in the olfactory bulb1–3. Here we investigate how this ordered representation is bulb to higher olfactory cortical centres. transformed in higher olfactory centres in mice. We have Mitral and tufted cells that innervate a single glomerulus were developed a tracing strategy to define the neural circuits that labelled by electroporation of tetramethylrhodamine (TMR)-dextran convey information from individual glomeruli in the olfactory under the guidance of a two-photon microscope. This technique labels bulb to the piriform cortex and the cortical amygdala. The spatial mitral and tufted cells that innervate a single glomerulus and is suffi- order in the bulb is discarded in the piriform cortex; axons from ciently robust to allow the identification of axon termini within mul- individual glomeruli project diffusely to the piriform without tiple higher order olfactory centres (Figs 1a–c, 2 and Supplementary apparent spatial preference. In the cortical amygdala, we observe Figs 1–4). Labelling of glomeruli in the olfactory bulbs of mice that broad patches of projections that are spatially stereotyped for indi- express GFP under the control of specific odorant receptor promoters vidual glomeruli. -
Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1 Jiyoung Park1,4*†, Athanasia Papoutsi3†, Ryan T
bioRxiv preprint doi: https://doi.org/10.1101/566588; this version posted March 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1 Jiyoung Park1,4*†, Athanasia Papoutsi3†, Ryan T. Ash2,4, Miguel A. Marin2, Panayiota Poirazi3* & Stelios M. Smirnakis4* 1Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 2Department of Neuroscience, Baylor College of Medicine, Houston, Texas 3Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology Hellas (FORTH), Vassilika Vouton, Heraklion, Crete, Greece 4Brigham and Women’s Hospital and Jamaica Plain VA Hospital, Harvard Medical School, Boston, MA †Equal contribution. * Correspondence: [email protected], [email protected], [email protected] Abstract: Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer- 2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2-3 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. -
Smell & Taste.Pdf
Smell and Taste 428 Special senses 1. SMELL (OLFACTION) 1.1 Overview Smell is the least Understood sense. It is mainly subjective. In dogs and other animals, it is more developed than humans. - There are dfferent stimuli that can be smelled such as: camphoraceous, musky, flora (flower), pepperminty, ethereal, pungent, putrid 1.2 Structure of Olfactory epithelium and bulb See the figure on the next page! 1.2.1 Olfactory mucous membrane It is the upper lining of the nasal cavity (near the septum), containing olfactory (odorant) receptors that are responsible for smelling. o Olfactory receptors are bipolar neurons which receive stimuli in the nasal cavity (through cilia) and transmits them through axons, leave the olfactory epithelium and travel into CNS (olfactory bulb). o Although they are nerve cells, olfactory receptor cells are replaced every 60 days or so, and they grow their axon into the correct place in CNS. Olfactory epithelium contains three types of cells (the olfactory receptors cells discussed) as well as two other types of cells: o Olfactory (Bowman’s) glands: produce mucus that dissolves odorants o Supporting cell o Basal cells: regenerate olfactory receptor cells. 1 Smell and Taste 428 1.2.2 Olfactory bulb The olfactory bulb is made up of nerves that receive olfactory signals from axons of olfactory receptor cells. These nerves are of two cell types: o Mitral cells (most important) (M) o Tufted cells (smaller than mitral cells) (T) Mitral and tufted cells release glutamate The synapse between the axons of olfactory receptor cells and dendrites of mitral cells occur in clusters called olphactory glomeruli (OG) In a glomerulus, about 1000 olfactory receptor axons converge onto 1 mitral cell. -
Improved Calcium Sensor Gcamp-X Overcomes the Calcium Channel Perturbations Induced by the Calmodulin in Gcamp
ARTICLE DOI: 10.1038/s41467-018-03719-6 OPEN Improved calcium sensor GCaMP-X overcomes the calcium channel perturbations induced by the calmodulin in GCaMP Yaxiong Yang 1,2,3,4, Nan Liu1,7, Yuanyuan He1, Yuxia Liu1, Lin Ge1, Linzhi Zou5, Sen Song1,4, Wei Xiong4,5 & Xiaodong Liu 1,2,3,4,5,6 2+ 1234567890():,; GCaMP, one popular type of genetically-encoded Ca indicator, has been associated with various side-effects. Here we unveil the intrinsic problem prevailing over different versions and applications, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (CaV1). GCaMP acts as an impaired apoCaM 2+ 2+ and Ca /CaM, both critical to CaV1, which disrupts Ca dynamics and gene expression. We then design and implement GCaMP-X, by incorporating an extra apoCaM-binding motif, effectively protecting CaV1-dependent excitation–transcription coupling from perturbations. GCaMP-X resolves the problems of detrimental nuclear accumulation, acute and chronic Ca2+ dysregulation, and aberrant transcription signaling and cell morphogenesis, while still demonstrating excellent Ca2+-sensing characteristics partly inherited from GCaMP. In summary, CaM/CaV1 gating and signaling mechanisms are elucidated for GCaMP side- effects, while allowing the development of GCaMP-X to appropriately monitor cytosolic, submembrane or nuclear Ca2+, which is also expected to guide the future design of CaM- based molecular tools. 1 Department of Biomedical Engineering, School of Medicine, X-Lab for Transmembrane Signaling Research, Tsinghua University, Beijing 100084, China. 2 School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. 3 Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 102402, China. -
Arc-Expressing Neuronal Ensembles
14070 • The Journal of Neuroscience, October 14, 2015 • 35(41):14070–14075 Brief Communications Arc-Expressing Neuronal Ensembles Supporting Pattern Separation Require Adrenergic Activity in Anterior Piriform Cortex: An Exploration of Neural Constraints on Learning X Amin MD. Shakhawat,1 XAli Gheidi,1 X Iain T. MacIntyre,1 Melissa L. Walsh,1 XCarolyn W. Harley,2 and XQi Yuan1 1Division of Biomedical Sciences, Faculty of Medicine, and 2Department of Psychology, Faculty of Science, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada Arc ensembles in adult rat olfactory bulb (OB) and anterior piriform cortex (PC) were assessed after discrimination training on highly similar odor pairs. Nonselective ␣- and -adrenergic antagonists or saline were infused in the OB or anterior PC during training. OB adrenergic blockade slowed, but did not prevent, odor discrimination learning. After criterion performance, Arc ensembles in anterior piriform showed enhanced stability for the rewarded odor and pattern separation for the discriminated odors as described previously. Anterior piriform adrenergic blockade prevented acquisition of similar odor discrimination and of OB ensemble changes, even with extended overtraining. Mitral and granule cell Arc ensembles in OB showed enhanced stability for rewarded odor only in the saline group. Pattern separation was not seen in the OB. Similar odor discrimination co-occurs with increased stability in rewarded odor representa- tions and pattern separation to reduce encoding overlap. The difficulty of similar discriminations may relate to the necessity to both strengthen rewarded representations and weaken overlap across similar representations. Key words: Arc; norepinephrine; odor discrimination; olfactory bulb; pattern separation; piriform cortex Significance Statement We show for the first time that adrenoceptors in anterior piriform cortex (aPC) must be engaged for adult rats to learn to discriminate highly similar odors. -
Clusters of Secretagogin-Expressing Neurons in the Aged Human Olfactory Tract Lack Terminal Differentiation
Clusters of secretagogin-expressing neurons in the aged human olfactory tract lack terminal differentiation Johannes Attemsa,1, Alan Alparb,c,1, Lauren Spenceb, Shane McParlanda, Mathias Heikenwalderd, Mathias Uhléne, Heikki Tanilaf, Tomas G. M. Hökfeltg,2, and Tibor Harkanyb,c,2 aInstitute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom; bEuropean Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; cDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, and gDepartment of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden; dInstitute of Virology, Technische Universität/Helmholtz Zentrum München, D-81675 Munich, Germany; eScience for Life Laboratory, Royal Institute of Technology, SE-17121 Stockholm, Sweden; and fDepartment of Neurology, Kuopio University Hospital and A. I. Virtanen Institute, University of Eastern Finland, FI-70211, Kuopio, Finland Contributed by Tomas G. M. Hökfelt, March 6, 2012 (sent for review November 10, 2011) Expanding the repertoire of molecularly diverse neurons in the olfactory system, we found secretagogin-positive (secretagogin+) human nervous system is paramount to characterizing the neuro- neurons in the RMS and olfactory bulb (16). Therefore, we hy- nal networks that underpin sensory processing. Defining neuronal pothesized that secretagogin may reveal previously undescribed identities is particularly timely in the human olfactory system, cellular identities and cytoarchitectural -
GPCR-Based Dopamine Sensors—A Detailed Guide to Inform Sensor Choice for in Vivo Imaging
International Journal of Molecular Sciences Review GPCR-Based Dopamine Sensors—A Detailed Guide to Inform Sensor Choice for In Vivo Imaging 1,2, 3,4, 4,5, Marie A. Labouesse y, Reto B. Cola y and Tommaso Patriarchi * 1 Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; [email protected] 2 Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA 3 Anatomy and Program in Neuroscience, University of Fribourg, 1700 Fribourg, Switzerland; [email protected] 4 Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland 5 Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland * Correspondence: [email protected]; Tel.: +41-044-635-59-21 These authors share equal co-first contribution. y Received: 10 September 2020; Accepted: 26 September 2020; Published: 28 October 2020 Abstract: Understanding how dopamine (DA) encodes behavior depends on technologies that can reliably monitor DA release in freely-behaving animals. Recently, red and green genetically encoded sensors for DA (dLight, GRAB-DA) were developed and now provide the ability to track release dynamics at a subsecond resolution, with submicromolar affinity and high molecular specificity. Combined with rapid developments in in vivo imaging, these sensors have the potential to transform the field of DA sensing and DA-based drug discovery. When implementing these tools in the laboratory, it is important to consider there is not a ‘one-size-fits-all’ sensor. Sensor properties, most importantly their affinity and dynamic range, must be carefully chosen to match local DA levels. -
Cortical Feedback Control of Olfactory Bulb Circuits
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron Article Cortical Feedback Control of Olfactory Bulb Circuits Alison M. Boyd,1,2 James F. Sturgill,1,2 Cindy Poo,1 and Jeffry S. Isaacson1,* 1Center for Neural Circuits and Behavior, Department of Neuroscience, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA 2These authors contributed equally to this work *Correspondence: [email protected] http://dx.doi.org/10.1016/j.neuron.2012.10.020 SUMMARY neuronal targets, effects on local circuits, and impact on OB odor processing in vivo are poorly understood. Olfactory cortex pyramidal cells integrate sensory In the OB, principal mitral and tufted (M/T) cells belonging to input from olfactory bulb mitral and tufted (M/T) cells unique glomeruli are activated by particular molecular features and project axons back to the bulb. However, the of individual odorants (Rubin and Katz, 1999; Soucy et al., impact of cortical feedback projections on olfactory 2009; Uchida et al., 2000). M/T cell output is strongly regulated bulb circuits is unclear. Here, we selectively express by local GABAergic interneurons (Shepherd et al., 2004). Indeed, channelrhodopsin-2 in olfactory cortex pyramidal odors can elicit purely inhibitory M/T cell responses reflecting a major role for circuits mediating lateral inhibition in the OB cells and show that cortical feedback projections (Cang and Isaacson, 2003; Davison and Katz, 2007; Yokoi excite diverse populations of bulb interneurons. Acti- et al., 1995). Reciprocal dendrodendritic synapses between vation of cortical fibers directly excites GABAergic M/T cell lateral dendrites and the distal dendritic spines of granule cells, which in turn inhibit M/T cells. -
Live Imaging of Calcium Dynamics During Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx
15026 • The Journal of Neuroscience, November 11, 2015 • 35(45):15026–15038 Development/Plasticity/Repair Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx X Mauricio Enrique Vargas,1,2 XYuya Yamagishi,3 Marc Tessier-Lavigne,3 and Alvaro Sagasti1 1Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California 90095, 2Jules Stein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, and 3Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065 Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. -
Exploring Olfactory Bulb Glomeruli with Serial Section Electron Microscopy Jennifer N
Exploring Olfactory Bulb Glomeruli with Serial Section Electron Microscopy Jennifer N. Bourne1 and Nathan E. Schoppa2 1. Department of Cell and Developmental Biology, 2. Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora USA Serial section electron microscopy (ssEM) is a powerful tool for analyzing complex structures in the brain. Cutting, collecting, imaging, and analyzing series of 100 – 200 ultrathin (~50 nm) sections of various brain regions can provide information about synaptic connectivity, subcellular organization, and surrounding cellular composition that would be more challenging to glean from lower resolution imaging techniques. In particular, areas where multiple cell types converge to process sensory information such as olfactory bulb glomeruli benefit from the use of ssEM. Receptors expressed on olfactory sensory neurons (OSNs) in the nasal epithelium bind to odorants and those OSNs expressing the same receptor all converge onto the same glomerulus in the olfactory bulb. Within a glomerulus, OSNs form excitatory synapses onto the dendrites of a variety of cell types, including the principal excitatory neurons, mitral and tufted cells that project to higher cortical areas. Rather than a simple relay station, physiology experiments have revealed that odor signals undergo complex processing within glomeruli from an assortment of inhibitory and neuromodulatory inputs [1]. However, the anatomical correlates of this signal processing have been difficult to decipher due to the intermingling of excitatory and inhibitory neuronal cell types and compartments (axons and dendrites) that can be indistinguishable on single sections. Analyses are further complicated by the presence of dendrodendritic synapses and gap junctions in addition to the typical axodendritic synapses [2]. -
Imaging Neural Activity in Worms, Flies and Mice with Improved Gcamp Calcium Indicators
Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators Lin Tian1, S. Andrew Hires1, Tianyi Mao1, Daniel Huber1, M. Eugenia Chiappe1, Sreekanth H. Chalasani2, Leopoldo Petreanu1, Jasper Akerboom1, Sean A. McKinney1,3, Eric R. Schreiter4, Cornelia I. Bargmann2, Vivek Jayaraman1, Karel Svoboda1, Loren L. Looger1g 1 Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA 2 Howard Hughes Medical Institute, Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA 3 Current address: The Stowers Institute, Kansas City, MO 64110, USA 4 Department of Chemistry, University of Puerto Rico – Río Piedras, San Juan, Puerto Rico 00931 gCorrespondence should be addressed to L. L. L. ([email protected]) 1 ABSTRACT Genetically encoded calcium indicators (GECIs) can be used to image activity in defined neuronal populations. However, current GECIs produce inferior signals compared to synthetic indicators and recording electrodes, precluding detection of low firing rates. We developed a single-wavelength GECI based on GCaMP2 (GCaMP3), with increased baseline fluorescence (3x), dynamic range (3x), and higher affinity for calcium (1.3x). GCaMP3 fluorescence changes triggered by single action potentials were detected in pyramidal cell dendrites, with signal-to-noise ratio and photostability significantly better than GCaMP2, D3cpVenus, and TN-XXL. In Caenorhabditis chemosensory neurons and the Drosophila antennal lobe, sensory stimulation-evoked fluorescence responses were significantly enhanced with the new indicator (4-6x). In somatosensory and motor cortical neurons in the intact mouse, GCaMP3 detected calcium transients with amplitudes linearly dependent on action potential number. Long-term imaging in the motor cortex of behaving mice revealed large fluorescence changes in imaged neurons over months.