A07

A07 Project movie

A07

In the 1st funding period, project A07 optimized cAMP sensors and photoactivatable ACs. In particular, project A07 successfully engineered PACmn , a membrane-anchored blue-light activated AC with no measurable dark activity. Recently, project A07 also confirmed that PACmn increases cAMP in astrocytes co-expressing Pink Flamindo, a cAMP sensor based on mApple that only correctly expresses/folds at or below 32°C. Also, an orange-red sensor for PKA, Booster-PKA, was used to confirm in neurons that PACmn, other than the previously used bPAC (from Beggiatoa), does not increase resting PKA activity in the dark. In addition to development of optogenetic tools, in the 1st funding period project A07 completed a detailed analysis of olfactory bulb astrocyte morphology. Further, Ca2+ signaling of olfactory bulb astrocytes upon norepinephrine stimulation had a modulatory effect on Gs-coupled cAMP signaling. In collaboration with project A16 (Dr. Hirnet and Prof. Friese), project A07 observed activation of microglial cells and microgliosis within the hippocampus in mouse EAE and will test the hypothesis that astrocytic function is altered in the hippocampus in EAE in the 2nd funding period. In neurons, project A07 studied the functional significance of cAMP signaling. Though cAMP has been linked to expression of immediate early genes, e.g. cFos, project A07 discovered that without a concomitant increase in neuronal firing and release of transmitters, cAMP does not directly induce cFos. These results became possible because only PACmn allows to raise cAMP in single neurons within a network of non-manipulated cells, which was impossible with previous approaches using pharmacologic and genetic manipulations. Project A07 also observed that raising cAMP only in astrocytes increases miniature excitatory postsynaptic currents, confirming project A07’s hypothesis that cAMP signaling in astrocytes modulates neuronal and synaptic function.

Dr Christine E. Gee

Selected publications (*equal contribution)

 

  1. Yang S*, Constantin OM*, Sachidanandan D*, Hofmann H, Kunz TC, Kozjak-Pavlovic V, Oertner TG, Nagel G, Kittel RJ, Gee CE*, Gao S* (2021) PACmn for improved optogenetic control of intracellular cAMP. BMC Biol 19, 227.
  2. Wiegert JS, Pulin M, Gee CE, Oertner TG (2018) The fate of hippocampal synapses depends on the sequence of plasticity-inducing events. eLife 7:e39151.
  3. Scheib U, Broser M, Constantin OM, Yang S, Gao S, Mukherjee S, Stehfest K, Nagel G, Gee CE*, Hegemann P* (2018) Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain. Nat Commun 9:2046
  4. Scheib U*, Stehfest K*, Gee CE*, Körschen HG, Fudim R, Oertner TG, Hegemann P (2015) The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Sci Signal 8:rs8. doi: 10.1126/scisignal.aab0611. *equal contribution
  5. Gee CE*, Peterlik D*, Neuhäuser C, Bouhelal R, Kaupmann K, Laue G, Uschold-Schmidt N, Feuerbach D, Zimmermann K, Ofner S, Cryan JF, van der Putten H, Fendt M, Vranesic I, Glatthar R & Flor PJ. (2014) Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the venus flytrap domain (VFTD) inhibits amygdala plasticity, stress and anxiety-related behavior. J Biol Chem 289:1097510987.
  6. Hoyer D, Dürst T, Fendt M, Jacobson LH, Betschart C, Hintermann S, Behnke D, Cotesta S, Laue G, Ofner S, Legangneux E & Gee CE (2013) Distinct effects of IPSU and suvorexant on mouse sleep architecture. Frontiers in Neurosci 7:235.
  7. Fendt, M, Imobersteg S, Peterlik D, Chaperon F, Mattes C, Wittmann C, Olpe H-R, Mosbacher J, Vranesic I, van der Putten PH, McAllister KH, Flor PJ & Gee CE (2013) Differential roles of mGlu7 and mGlu8 in amygdala-dependent behavior and physiology. Neuropharmacology 72:215-233.
  8. Mang GM, Dürst T, Bürki H, Imobersteg S, Abramowski D, Schuepbach E, Hoyer D, Fendt M & Gee CE (2012) The dual orexin receptor antagonist almorexant induces sleep and decreases orexin induced locomotion by blocking orexin 2 receptors. SLEEP 35:1625-1635.
  9. Matsumoto-Miyai K, Sololowska E, Zurlinden A, Gee CE, Lüscher D, Hettwer S, Wölfel J, Ladner AP, Ster J, Gerber U, Rülicke T, Kunz B & P Sonderegger (2009) Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage. Cell 136:1161-1171.
  10. Gee CE, Benquet P, Gerber U (2003) Group I metabotropic glutamate receptors activate a calcium-sensitive transient receptor potential-like conductance in rat hippocampus. J Physiol 546:655-64.

Prof. Dr Christian Lohr

Selected publications (*equal contribution)

 

  1. Fischer T, Prey J, Eschholz L, Rotermund N, Lohr C (2021) Norepinephrine-induced calcium signaling and store-operated calcium entry in olfactory bulb astrocytes. Front Cell Neurosci 15:639754.
  2. Beiersdorfer A, Wolburg H, Grawe J, Scheller A, Kirchhoff F, Lohr C (2020) Sublamina-specific organization of the blood brain barrier in the mouse olfactory nerve layer. Glia 68:631-645
  3. Beiersdorfer A, Scheller A, Kirchhoff F, Lohr C (2019) Panglial gap junctions between astrocytes and olfactory ensheathing cells mediate transmission of Ca2+ transients and neurovascular coupling. GLIA 67:1385-1400.
  4. Rotermund N, Winandy S, Fischer T, Schulz K, Fregin T, Alstedt N, Buchta M, Bartels J, Carlström M, Lohr C, Hirnet D (2018) Adenosine A1 receptor activates background potassium channels and modulates information processing in olfactory bulb mitral cells. J Physiol 596:717-733
  5. Stavermann M, Meuth P, Doengi M, Thyssen A, Deitmer JW, Lohr C (2015) Calcium-induced calcium release and gap junctions mediate large-scale calcium waves in olfactory ensheathing cells in situ. Cell Calcium 58:215-225.
  6. Thyssen A, Hirnet D, Wolburg H, Schmalzing G, Deitmer JW, Lohr C (2010) Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling. Proc Natl Acad Sci USA107:15258-15263
  7. Doengi M, Hirnet D, Coulon P, Pape HC, Deitmer JW, Lohr C (2009) GABA uptake-dependent Ca2+ signaling in olfactory bulb astrocytes. Proc Natl Acad Sci USA 106:17570-17575.
  8. Doengi M, Deitmer JW, Lohr C (2008) New evidence for purinergic signaling in the olfactory bulb: A2A and P2Y1 receptors mediate intracellular calcium release in astrocytes. FASEB J 22:2368-2378.
  9. Singaravelu K, Lohr C, Deitmer JW. Regulation of store-operated calcium entry by calcium-independent phospholipase A2 in rat cerebellar astrocytes. J Neurosci. 2006; 26, 9579-9592.
  10. Lohr C, Heil JE, Deitmer JW. Blockage of voltage-gated calcium signaling impairs migration of glial cells in vivo. GLIA 2005; 50, 198-211.

Our Team

Prof. Dr Christian Lohr

Universität Hamburg
Faculty of Mathematics, Informatics and Natural Sciences
Department Biology
Institute of Zoology
Neurophysiology
Martin-Luther-King-Platz 3
20146 Hamburg

Dr. Christine Gee

Dept. of Synaptic Physiology

Center for Molecular Neurobiology Hamburg (ZMNH)

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Oana Constantin

Dept. of Synaptic Physiology

Center for Molecular Neurobiology Hamburg (ZMNH)

University Medical Center Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de