Group leader: Jean-René Martin

Functional Brain Imaging & Behavior

In brief

Aging, longevity, and neurodegenerative diseases are major concerns of public health. Our team is focalized on the characterization of the role of a new snoRNA (jouvence) that we have identified in Drosophila. Jouvence increases lifespan and protects against neurodegenerative lesions. It is required in the epithelium of the gut, revealing a new gut-brain axis. Since the snoRNAs are well conserved through evolution, we have identified its homologue in human, and we are currently characterizing its role in human culture cells. In parallel, using the in-vivo functional brain imaging approach that we have developed in our laboratory, based on bioluminescence, we study the role of the particular retrograde peak of Ca2+-activity in the Mushroom-Bodies, and more precisely its role in anaesthesia, whose represents a new model/system to study the consciousness.

The thematic of my team concerns the study of the neural bases of some behavior, as locomotor activity and more recently of olfaction, using a genetically tractable model system, the Drosophila. We use pluridisciplinary approaches, from genes characterization (molecular cloning) up to the whole integrated function, the locomotor activity and olfaction.
Methodologically, this implies the genetic and molecular biology, the neuroanatomy, the behavioral analysis and recently, the in-vivo functional brain imaging, by a bioluminescence approach. We have developed a video-tracking paradigm permitting to precisely quantifying the locomotor activity and allowing revealing its multiple complex parameters. More recently, we have develop a new in-vivo brain imaging approach, in bioluminescence, based on a chimeric protein (GFP-aequorin), allowing to record the neuronal activity.
Three axes are currently studied, in parallel.

Thematic 1

In-vivo functional brain imaging, by bioluminescence.

This technique allows recording the neuronal calcium activity, in-vivo, in continue, from different brain structures, either superficially or deeply located, in semi-behavioral conditions. This approach opens several perspectives, as:

a) characterization of the olfactory response following natural stimuli (odors), at different levels of the olfactory circuitry: first, in the olfactory receptor neurons (ORNs) in the antennal lobes, second, in the projections neurons (PNs), and third, in the Mushrooms-bodies (a structure implicated in the olfactory learning and memory). More particularly, we have described an olfactory adaptation process occurring in the axon terminal of the ORNs (within the antennal lobes), and we are currently characterizing such physiological phenomenon.

b) characterization of the delayed secondary response specifically in the Mushroom-Bodies lobes (axonal projections) induced by the nicotine (an acetylcholine agonist).

c) characterization of the neuronal activity in the ellipsoid-body, in relation to the locomotor activity.

d) Construction of anatomo-functionnal maps (build a functional Atlas) of the general activity (spontaneous or induced) of the overall brain considered as an ensemble, through a pan-neuronal expression of the GFP-aequorin.

Thematic 2

Study of the role of the Central Complex (a premotor center) through the genetic and molecular characterization of the line P[GAL4]4C, specifically expressed in the ellipsoid-body (a substructure of the Central complex).

Thematic 3

Characterization of the brain structures implicated in the centrophobism and in the thigmotaxis, two components of the spatial orientation.

Selected publications

  • Soulé S, Mellottée L, Arab A, Chen C, Martin JR. (2020). Jouvence a small nucleolar RNA required in the gut extends lifespan in Drosophila. Nat Commun 11, 987. DOI: 10.1038/s41467-020-14784-1
  • Lark A, Kitamoto T, Martin JR. (2017). Modulation of neuronal activity in the Drosophila mushroom body by DopEcR, a unique dual receptor for ecdysone and dopamine. Biochim Biophys Acta, Mol. Cell Res., 1864, 1578-1588. DOI: 10.1016/j.bbamcr.2017.05.015
  • Murmu MS, Martin, JR (2016). Interaction between cAMP and intracellular Ca2+-signaling pathways during odor-perception and adaptation in Drosophila. Biochim Biophys Acta, Mol. Cell Res., 1863, 2156-2174. DOI: 10.1016/j.bbamcr.2016.05.014
  • Lark AR, Kitamoto T, Martin JR (2016). In Vivo Functional Brain Imaging Approach Based on Bioluminescent Calcium Indicator GFP-aequorin. J Vis Exp., 107, doi: 10.3791/53705. DOI: 10.3791/53705
  • Pierre Pavot, Elena Carbognin, Jean-René Martin (2015). PKA and cAMP/CNG Channels Independently Regulate the Cholinergic Ca2+-Response of Drosophila Mushroom Body Neurons. eNeuro, DOI: 10.1523/ENEURO.0054-14.2015
  • Martin J.R, Rogers KL, Chagneau C, Brûlet P (2007) In vivo Bioluminescence Imaging of Ca2+ Signalling in the Brain of Drosophila. PLoS ONE 2(3): e275. DOI: 10.1371/journal.pone.0000275
  • Martin, J.-R. (2004). A portrait of locomotor behaviour in Drosophila determined by a video-tracking paradigm. Behav. Process., 67, 207-219. DOI: 10.1016/j.beproc.2004.04.003
  • Martin, J.R., Faure, F., and Ernst, R. (2002). The Power Law Distribution for Walking-Time Intervals Correlates with the Ellipsoid Body in Drosophila. J. Neurogenetics, 15, 1-15. DOI: 10.3109/01677060109167377
Peer-reviewed Articles

• Flaria El-Khoury, Jérôme Bignon, Jean-René Martin (2020). Jjouvence, a new human snoRNA involved in the control of cell proliferation. BMC Genomics, 21(1):817. https://doi.org/10.1186/s12864-020-07197-3
• Soulé S, Mellottée L, Arab A, Chen C, Martin JR. (2020). Jouvence a small nucleolar RNA required in the gut extends lifespan in Drosophila. Nat Commun 11, 987. https://doi.org/10.1038/s41467-020-14784-1
• Benjamin Kottler, Vincenzo G. Fiore, Zoe N. Ludlow, Edgar Buhl, Gerald Vinatier, Richard Faville, Danielle C. Diaper, Alan Stepto, Jonah Dearlove, Yoshitsugu Adachi, Sheena Brown, Chenghao Chen, Daniel A. Solomon, Katherine E. White, Dickon M. Humphrey, Sean M. Buchanan, Stephan J. Sigrist, Keita Endo, Kei Ito, Benjamin de Bivort, Ralf Stanewsky, Raymond J. Dolan, Jean-Rene Martin, James J. L. Hodge, Nicholas J. Strausfeld, Frank Hirth. (2017). A lineage-related reciprocal inhibition circuitry for sensory-motor action selection. bioRxiv (100420; https://doi.org/10.1101/100420)
• Lark A, Kitamoto T, Martin JR. (2017). Modulation of neuronal activity in the Drosophila mushroom body by DopEcR, a unique dual receptor for ecdysone and dopamine. Biochim Biophys Acta, Mol. Cell Res., 1864, 1578-1588.
• Murmu MS, Martin, JR (2016). Interaction between cAMP and intracellular Ca2+-signaling pathways during odor-perception and adaptation in Drosophila. Biochim Biophys Acta, Mol. Cell Res., 1863, 2156-2174.
• Lark AR, Kitamoto T, Martin JR (2016). In Vivo Functional Brain Imaging Approach Based on Bioluminescent Calcium Indicator GFP-aequorin. J Vis Exp., 107, doi: 10.3791/53705.
• Pierre Pavot, Elena Carbognin, Jean-René Martin (2015). PKA and cAMP/CNG Channels Independently Regulate the Cholinergic Ca2+-Response of Drosophila Mushroom Body Neurons. eNeuro, DOI: 10.1523/ENEURO.0054-14.2015
• Minocci, D, Carbognin, E Murmu, M, Martin, JR (2013). In vivo functional calcium imaging of induced or spontaneous activity in the fly brain using a GFP-apoaequorin-based bioluminescent approach. Biochim Biophys Acta., Mol. Cell Res., 1833, 1632-1640.
• Picaud, S., Martin, JR., Karplus, E., Moreau, M. (2013). A tribute to Philippe Brûlet (1947-2012). In: European Calcium Society (ECS) Letter. May 2013. (revue sans comité de lecture)
• Martin, JR. (2012). The revenge of aequorin. In: European Calcium Society (ECS) Letter. May, 2012. (revue sans comité de lecture)
• Martin, JR. (2012). In vivo functional brain imaging using a genetically encoded Ca2+-sensitive bioluminescence reporter, GFP-aequorin. In: “Genetically Encoded Functional Indicators”. Ed. JR Martin. Neuromethods, Volume 72, Springer Science+Business Media, LLC, New York, NY, USA. (Book chapter)
• Martin, JR. (2012). Editor: “Genetically Encoded Functional Indicators”. Ed. JR Martin. Neuromethods, Volume 72, Springer Science+Business Media, LLC, New York, NY, USA. (Editor)
• Murmu MS, Stinnakre J, Réal E, Martin JR (2011). Calcium-stores mediate adaptation in axon terminals of Olfactory Receptor Neurons in Drosophila. BMC Neurosci., Oct 24;12(1):105.
• Inoshita T, Martin JR, Marion-Poll F, Ferveur JF (2011). Peripheral, Central and Behavioral Responses to the Cuticular Pheromone Bouquet in Drosophila melanogaster Males. PLoS One, 6(5):e19770.
• Murmu MS, Stinnakre J, Martin JR (2010). Presynaptic Ca2+-stores contribute to odor-induced response in Drosophila olfactory receptor neurons. J. Exp. Biol., 213, 4163-4173.
• Jones G, Jones D, Li X, Tang L, Ye L, Teal P, Riddiford L, Sandifer C, Borovsky D, Martin JR. (2010). Activities of natural methyl farnesoids on pupariation and metamorphosis of Drosophila melanogaster. J Insect Physiol., 56, 1456-1464.
• Kahsai, L., Martin, J-R, Winther, A.M.E. (2010). Neuropeptides in the Drosophila central complex in modulation of locomotor behavior. J. Exp. Biol., 213, 2256-2265.
• Jones D., Jones G., Teal P., Hammac C., Messmer L., Osborne K., Belgacem Y. H., Martin J.-R. (2009). Suppressed production of methyl farnesoid hormones yields developmental defects and lethality in Drosophila larvae. Gen. Comp. Endocrinol., 165, 244-254.
• Lebreton, S., Martin, J.R. (2009). Mutations Affecting the cAMP Transduction Pathway
Disrupt the Centrophobism Behavior. J. of Neurogenetics, 23, 225-234.
• Martin, J.R. (2008). In vivo Brain Imaging: Fluorescence or Bioluminescence, Which to Choose ? (a review) J. of Neurogenetics, 22, 285-307.
• Rogers, K.L., Martin, J.R., Renaud, O., Karplus, E., Nicola, M.A., Nguyen, M., Picaud, S., Shorte, S.L., Brûlet, P. (2008). EMCCD based bioluminescence recording of single-cell Ca2+. J. of Biomedical Optics, 13 (3), 1-10.
• Martin J.R, Rogers KL, Chagneau C, Brûlet P (2007) In vivo Bioluminescence Imaging of Ca2+ Signalling in the Brain of Drosophila. PLoS ONE 2(3): e275.
• Meunier, N., Belgacem, H. Y. & Martin, J.-R. (2007). Regulation of feeding behavior and locomotor activity by takeout, in Drosophila. J. Exp. Biol., 210, 1424-1434.
• Hadj Belgacem, Y., Martin, J.-R. (2007). Hmgcr in the Corpus Allatum Controls Sexual Dimorphism of Locomotor Activity and Body Size via the Insulin Pathway in Drosophila. PLoS ONE 2(1):e187.
• Hadj Belgacem, Y., Martin, J.-R. (2006). Disruption of Insulin Pathways Alters Trehalose Level and Abolishes Sexual Dimorphism in Locomotor Activity in Drosophila. J. Neurobiol., 66, 19-32.
• Zordan, M.A., Massironi, M., Ducato, M.G., Kronnie, T.T., Costa, R., Reggiani, C., Chagneau, C., Martin, J.-R., Megighian, A. (2005). The Drosophila CAKI/CMG protein, a homolog of human CASK, is essential for regulation of neurotransmitter vesicle release. J. Neurophysiol., 94, 1074-1083.
• Besson, M., Martin, J.R. (2005). Centrophobism/Thigmotaxis, a new role for the Mushroom Bodies in Drosophila. J. Neurobiol., 62, 386-396.
• Isabel, I., Martin, J.-R., Chidami, S., Veenstra, J.A., Rosay, P. (2004). Extension of life-span in starved Drosophila melanogaster by ablation of AKH-producing neuroendocrine cells. Am J Physiol Regul Integr Comp Physiol., 288, R531-538.
• Kowalski, S., Aubin, T., Martin, J.-R. (2004). Courtship song in Drosophila: a differential effect on male-female locomotor activity. Can. J. Zool., 82, 1258-1266.
• Godenschwege, T.A., Reisch, D., Diegelmann S., Eberle K., Heisenberg, M., Hoppe, V., Hoppe, J., Klagges, B.R.E., Martin, J.-R., Nikitina, E.A., Putz, G., Reifegerste, R., Reisch, N., Riester, J., Schaupp, M., Scholz, H., Schwärzel, M., Werner, U., Buchner, S., Buchner, E. (2004). Synapsin knock-out flies are impaired in complex behaviour. Eur. J. Neurosci., 20, 611-622.
• Martin, J.-R. (2004). A portrait of locomotor behaviour in Drosophila determined by a video-tracking paradigm. Behav. Process., 67, 207-219.
• Martin, J.R. (2003). Locomotor activity: a complex behavioural trait to unravel. Behav. Process., 64, 145-160.
• Suster, M.L., Martin, J.-R., Sung, C., Robinow, S. (2003). Targeted expression of tetanus toxin reveals sets of neurons involved in larval locomotion in Drosophila. J. Neurobiol., 55, 233-246.
• Hadj Belgacem, Y., Martin, J.-R., (2002). Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila. Proc. Nat. Acad. Sci. USA., 99, 15154-15158.
• Martin, J.R., Keller, A., Sweeney, S. (2002). Targeted Expression of Tetanus Toxin: A New Tool to Study the Neurobiology of Behavior. Advances in Genetics, 47, 1-48.
• Martin, J.R., Faure, F., and Ernst, R. (2002). The Power Law Distribution for Walking-Time Intervals Correlates with the Ellipsoid Body in Drosophila. J. Neurogenetics, 15, 1-15.
• Gatti, S., Ferveur J.F., Martin, J.R. (2000). Genetic Identification of Neurones Controlling a Sexually Dimorphic Behavior. Current Biology, 10, 667-670.
• Martin, J.R., Ernst, R., and M. Heisenberg (1999). Temporal Pattern of Locomotor Activity in Drosophila melanogaster. J. Comp. Physiol A, 184, 73-84.
• Martin J.R., Raabe T., and M. Heisenberg (1999) Central Complex Substructures Are Required for the Maintenance of Locomotor Activity in Drosophila melanogaster. J. Comp. Physiol A, 185, 277-288.
• Martin, J.R., Ernst, R., and M. Heisenberg (1998). Mushroom Bodies suppress locomotor activity in Drosophila melanogaster. Learning & Memory, 5, 179-191.
• Martin, J.R., and Ollo, R. (1996). A new Drosophila Ca2+-calmodulin-dependent protein kinase (Caki) is localized in the central nervous system and implicated in walking speed. EMBO J. 15, 1865-1876.
• Martin, J.R., Raibaud, A., and Ollo, R. (1994). Terminal pattern elements in Drosophila embryo induced by the torso-like protein. Nature, 367, 741-745.
• Jacob, Y., Sather, S., Martin, J.R., Ollo, R. (1991). Analysis of Krüppel control elements reveals that localized expression results from the interaction of multiple sub-elements. Proc. Natl. Aca. Sci. USA 88, 5912-5916.
• Martin, J.R., Harvey, D., Montpetit, C. (1987). La mammillite herpétique bovine au Québec. Can. Vet. J., 28, No. 8.
• Higgins, R., Martin, J.R., Larouche, Y., Goyette, G. (1987). Mastitis caused by haemophilus somnus in a dairy cow. Can. Vet. J., 28, No. 3.