Mayer Philipp, Sivakumar Nandhini, Pritz Michael, Varga Matjia, Mehmann Andreas, Lee Seunghyun, Salvatore Alfredo, Magno Michele, Pharr Matt, Johannssen Helge C., Troester Gerhard, Zeilhofer Hanns Ulrich, Salvatore Giovanni Antonio (2019), Flexible and Lightweight Devices for Wireless Multi-Color Optogenetic Experiments Controllable via Commercial Cell Phones, in Frontiers in Neuroscience
, 13, 1-14.
Pagani Martina, Albisetti Gioele W., Sivakumar Nandhini, Wildner Hendrik, Santello Mirko, Johannssen Helge C., Zeilhofer Hanns Ulrich (2019), How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch, in Neuron
, 103(1), 102-117.e5.
Albisetti Gioele W., Pagani Martina, Platonova Evgenia, Hösli Ladina, Johannssen Helge C., Fritschy Jean-Marc, Wildner Hendrik, Zeilhofer Hanns Ulrich (2019), Dorsal Horn Gastrin-Releasing Peptide Expressing Neurons Transmit Spinal Itch But Not Pain Signals, in The Journal of Neuroscience
, 39(12), 2238-2250.
Ralvenius William T., Neumann Elena, Pagani Martina, Acuña Mario A., Wildner Hendrik, Benke Dietmar, Fischer Nina, Rostaher Ana, Schwager Simon, Detmar Michael, Frauenknecht Katrin, Aguzzi Adriano, Hubbs Jed Lee, Rudolph Uwe, Favrot Claude, Zeilhofer Hanns Ulrich (2018), Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors, in Nature Communications
, 9(1), 3230-3230.
Neumann Elena, Ralvenius William T., Acuña Mario A., Rudolph Uwe, Zeilhofer Hanns Ulrich (2018), TP003 is a non-selective benzodiazepine site agonist that induces anxiolysis via α2GABAA receptors, in Neuropharmacology
, 143, 71-78.
Huang Jing, Polgár Erika, Solinski Hans Jürgen, Mishra Santosh K., Tseng Pang-Yen, Iwagaki Noboru, Boyle Kieran A., Dickie Allen C., Kriegbaum Mette C., Wildner Hendrik, Zeilhofer Hanns Ulrich, Watanabe Masahiko, Riddell John S., Todd Andrew J., Hoon Mark A. (2018), Circuit dissection of the role of somatostatin in itch and pain, in Nature Neuroscience
, 21(5), 707-716.
Albisetti Gioele W, Ghanem Alexander, Foster Edmund, Conzelmann Karl-Klaus, Zeilhofer Hanns Ulrich, Wildner Hendrik (2017), Identification of Two Classes of Somatosensory Neurons That Display Resistance to Retrograde Infection by Rabies Virus., in The Journal of neuroscience : the official journal of the Society for Neuroscience
, 37(43), 10358-10371.
Haenraets Karen, Foster Edmund, Johannssen Helge, Kandra Vinnie, Frezel Noémie, Steffen Timothy, Jaramillo Valeria, Paterna Jean-Charles, Zeilhofer Hanns Ulrich, Wildner Hendrik (2017), Spinal nociceptive circuit analysis with recombinant adeno-associated viruses: the impact of serotypes and promoters., in Journal of neurochemistry
, 142(5), 721-733.
Zeilhofer Hanns Ulrich, Acuña Mario A, Gingras Jacinthe, Yévenes Gonzalo E (2017), Glycine receptors and glycine transporters: targets for novel analgesics?, in Cellular and molecular life sciences : CMLS
Müller Herde Adrienne, Benke Dietmar, Ralvenius William T, Mu Linjing, Schibli Roger, Zeilhofer Hanns Ulrich, Krämer Stefanie D (2017), GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [18F]flumazenil PET., in NeuroImage
, 150, 279-291.
Ralvenius William T, Acuña Mario A, Benke Dietmar, Matthey Alain, Daali Youssef, Rudolph Uwe, Desmeules Jules, Zeilhofer Hanns Ulrich, Besson Marie (2016), The clobazam metabolite N-desmethyl clobazam is an α2 preferring benzodiazepine with an improved therapeutic window for antihyperalgesia., in Neuropharmacology
, 109(10), 366-375.
Acuña Mario A, Yévenes Gonzalo E, Ralvenius William T, Benke Dietmar, Di Lio Alessandra, Lara Cesar O, Muñoz Braulio, Burgos Carlos F, Moraga-Cid Gustavo, Corringer Pierre-Jean, Zeilhofer Hanns Ulrich (2016), Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain., in The Journal of clinical investigation
, 126(7), 2547-60.
Zeilhofer Hanns Ulrich, Ralvenius William T, Acuña Mario A (2015), Restoring the spinal pain gate: GABA(A) receptors as targets for novel analgesics., in Advances in pharmacology (San Diego, Calif.)
, 73, 71-96.
Ralvenius William T, Benke Dietmar, Acuña Mario A, Rudolph Uwe, Zeilhofer Hanns Ulrich (2015), Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype., in Nature communications
, 6, 6803.
Foster Edmund, Wildner Hendrik, Tudeau Laetitia, Haueter Sabine, Ralvenius William T, Jegen Monika, Johannssen Helge, Hösli Ladina, Haenraets Karen, Ghanem Alexander, Conzelmann Karl-Klaus, Bösl Michael, Zeilhofer Hanns Ulrich (2015), Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch., in Neuron
, 85(6), 1289-304.
Besides pain, itch is a second sensation that has evolved to protect higher organisms from potential environmental harm. Under physiological conditions, both sensations originate from the activation of plasma membrane receptors on primary afferent sensory neurons that convey these signals to the spinal cord and brainstem. During the last decade, several receptors have been identified which are specifically activated by pruritic (itch-inducing) stimuli. Less is known about downstream dorsal horn circuits and the spinal processing of itch-related signals. Two neuropeptides, gastrin releasing peptide (GRP) and b-type natriuretic peptide (BNP) have been considered as spinal messengers of itch. The present proposal addresses a dorsal horn neuronal circuit involved in itch processing and its control by inhibitory interneurons and itch-related neuropeptides. The starting point of these studies will be GRP expressing dorsal horn neurons, which are critical for the spinal relay of some forms of itch. Diphtheria toxin-mediated ablation of these neurons reduced chloroquine-induced itch responses in behaving mice. Additional preliminary data from rabies virus-based retrograde tracing experiments indicate that the majority of spinal interneurons presynaptic to GRP neurons are inhibitory (presumably combined GABA/glycinergic) interneurons of the deep dorsal horn. Here, we propose to use rabies virus-based retrograde tracing experiments, targeted electrophysiological recordings in spinal cord slices in combination with optogenetics, in vivo 2-photon recordings, and behavioural tests to elucidate an itch-related dorsal horn neuronal circuit and its control by inhibitory interneurons. From these experiments, we expect to gain novel insights into the spinal processing of this still poorly understood sense.