Frezel N, Platonova E, Voigt F F, Mateos J M, Kastli R, Ziegler U, Karayannis T, Helmchen F, Wildner H, Zeilhofer H U (2020), In-Depth Characterization of Layer 5 Output Neurons of the Primary Somatosensory Cortex Innervating the Mouse Dorsal Spinal Cord, in Cerebral Cortex Communications
, 1(1), 1-16.
ZeilhoferHanns Ulrich, GanleyRobert (2020), Dorsal horn pain mechanisms, in Wood John N., Wood John N. (ed.), Oxford University Press, Oxford, 1-29.
Voigt Fabian F., Kirschenbaum Daniel, Platonova Evgenia, Pagès Stéphane, Campbell Robert A. A., Kastli Rahel, Schaettin Martina, Egolf Ladan, van der Bourg Alexander, Bethge Philipp, Haenraets Karen, Frézel Noémie, Topilko Thomas, Perin Paola, Hillier Daniel, Hildebrand Sven, Schueth Anna, Roebroeck Alard, Roska Botond, Stoeckli Esther T., Pizzala Roberto, Renier Nicolas, Zeilhofer Hanns Ulrich, Karayannis Theofanis, Ziegler Urs, Batti L, Holtmaat Anthony, Luscher Christian, Aguzzi Adriano, Helmchen Fritjof (2019), The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue, in Nature Methods
, 16(11), 1105-1108.
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.
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
, 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.
The present proposal addresses dorsal horn neuronal circuits involved in itch processing and their control by inhibitory interneurons, inhibitory neurotransmitters and itch-related neuropeptides. For the up-coming funding period, we propose to focus on the following three aims: (1) Cellular mechanisms underlying the role of b-type natriuretic peptide (BNP) in spinal itch transmission. BNP is a potential peptide messenger contributing to transmission between pruritoceptive sensory neurons (primary pruritoceptors) and second order itch neurons in the spinal dorsal horn. It is mainly expressed in the neurotensin (NTS) positive population of primary pruritoceptors. Using optogenetic stimulation of NTS positive axon terminals and targeted recordings from second order itch (GPR positive) neurons in mouse spinal cord slices we will investigate the role of BNP at the first synapse of the itch pathway. (2) Identification of subpopulations of glycinergic neurons controlling spinal itch circuits. Using retrograde monosynaptic tracing, we found that second order itch neurons receive synaptic input from local inhibitory and excitatory interneurons. Consistent with this inhibitory innervation, ablation and silencing of inhibitory glycinergic (GlyT2-positive) deep dorsal horn neurons induced aversive behaviour reminiscent of chronic itch. Using cre/dre intersectional gene targeting, we will further dissect the glycinergic population of dorsal horn neurons to narrow down on more restricted inhibitory neuron populations that control itch. (3) Subtypes of GABA-A receptors controlling itch responses - beyond diversity of the alpha subunit. While the great majority of benzodiazepine-sensitive GABA-A receptors contain a gamma2 subunit, we found that the spinal antipruritic actions of several benzodiazepine site agonists are maintained in the absence of gamma2 subunits. Preliminary gene expression analyses suggest that primary sensory neurons and central neurons of the spinal dorsal horn express significant amounts gamma1 subunits in addition to gamma2. We have meanwhile generated gamma1 (Gabrg1)-deficient mice and will perform comprehensive comparisons of these mice with wild-type mice and mice lacking gamma2 subunits from the spinal cord. From these experiments, we expect to gain novel insights into the spinal control of the still poorly understood itch sense.