AG Jun. Prof. Kätzel

Quelle: E. Eberhardt, Universität Ulm

Forschung

Research Focus: Circuits, Drugs and Schizophrenia

We focus on the understanding of the neural mechanisms that lead to schizophrenia. Schizophrenia is a psychiatric disease affecting close to 1 % of the population and accounting for 25 % of psychiatric hospital beds. It is characterized by "positive" symptoms such as halluzinations and delusions, but also by "cognitive" and "negative" symptoms like deficits in working memory, attention, cognitive flexibility, social interaction and motivation. It is such cognitive and negative symptoms that hardly respond to currently available drug therapy and therefore represent the focus of our translational research efforts.

Our goals are to support the development of novel therapeutical approches by:

  • understanding where symptoms of schizophrenia originate from at the neural circuit level.
  • develop better preclinical models of schizophrenia and better biomarkers for prediction of clinical efficacy.
  • understand how existing drugs and novel drug candidates actually work at the circuit level.
  • identify cellular and circuit targets for therapy.

Our approach is to combine state-of-the-art techniques of neural circuit analysis, including:

  • optogenetic and chemogenetic circuit manipulation (i.e. the remote control of genetically specified cell types).
  • in vivo electrophysiological technique.
  • behavioural analysis and behavioural pharmacology.
  • transgenic models of schizophrenia.

Publikationen

Teutsch J, Kätzel D (2019): Operant Assessment of DMTP Spatial Working Memory in Mice. Front Behav Neurosci. 2019 Aug 27;13:193. doi: 10.3389/fnbeh.2019.00193.

Bygrave AM, Jahans-Price T, Wolff AR, Sprengel R, Kullmann DM, Bannerman DM, Kätzel D. (2019): Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1., Transl Psychiatry. 2019 Apr 18;9(1):142. doi: 10.1038/s41398-019-0471-0.

Liss B, Kätzel D (2019): Kleinhirn, in Brandes R, Lang F, Schmidt RF: Physiologie des Menschen: mit Pathophysiologie, Springer-Verlag. ISBN 978-3-662-56467-7 Link

Jendryka M, Palchaudhuri M, Ursu D, van der Veen B, Liss B, Kätzel D, Nissen W, Pekcec A (2019): Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice. Scientific Reports 9:4522. doi: 10.1038/s41598-019-41088-2.

Bygrave AM, Masiulis S, Kullmann DM, Bannerman DM, Kätzel D (2018): Gene-Environment Interaction in a Conditional NMDAR-Knockout Model of Schizophrenia. Front Behav Neurosci. doi: 10.3389/fnbeh.2018.00332.

Grimm CM, Aksamaz S, Schulz S, Teutsch J, Sicinski P, Liss B and Kätzel D (2018): Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model of ventral hippocampal hyperactivity. Translational Psychiatry 8:212. doi:10.1038/s41398-018-0268-6.

Wolff AR, Bygrave AM, Sanderson DJ, Boyden DS, Bannerman DM, Kullmann DM, Kätzel D (2018): Optogenetic induction of the schizophrenia-related endophenotype of ventral hippocampal hyperactivity causes rodent correlates of positive and cognitive symptoms; Sci Rep. 2018 Aug 27;8(1):12871. doi: 10.1038/s41598-018-31163-5.

De Bruyckere E, Simon R, Nestel S, Heimrich B, Kätzel D, Egorov AV, Liu P, Jenkins NA, Copeland NG, Schwegler H, Draguhn A, Britsch S (2018): Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2; Front Mol Neurosci. 2018 Apr 5;11:103. doi: 10.3389/fnmol.2018.00103

Kohl MM, Kätzel D (2017): Optogenetic mapping of neuronal connections and their plasticity, in Appasani K (ed.): Optogenetics: from neuronal function to mapping and disease biology, Cambridge University Press, 2017. Link

Bygrave AM, Masiulis S, Nicholson E, Berkemann M, Barkus C, Sprengel R, Harrison P, Kullmann DM, Bannermann DM, Kätzel D (2016): Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801; Translational Psychiatry (2016) 6, e778; doi: 10-1038/tp.2016.44; published online: 12 April 2016.

Anastasiades PG, Marques-Smith A, Lyngholm D, Lickiss T, Raffiq S, Kätzel D, Miesenböck G, Butt SJ (2016): GABAergic interneurons form transient, layer-specific circuits in early postnatal neocortex; Nature Communications February 04; doi:10.1038/ncomms10584

Kätzel D, Kullmann D (2015): Optogenetic and chemogenetic tools for drug discovery in schizophrenia. Book chapter in: Drug discovery for schizophrenia. RSC Publishing. Lipina T, Roder J (eds.). ISBN 978-1-78262-026-6.

Kätzel D, Nicholson E, Schorge S, Walker MC, Kullmann DM (2014): Chemical-genetic attenuation of focal neocortical seizures; Nature Communications May 27; doi: 10.1038/ncomms4847. 

Kätzel D, Miesenböck G (2014): Experience-dependent rewiring of specific inhibitory connections in adult neocortex. PLoS Biol, February 25; 12(2): e1001798. doi: 10.1371/journal.pbio.1001798. 

Kätzel D, Zemelman BV, Buetfering C, Wölfel M, Miesenböck G (2011): The columnar and laminar organization of inhibitory connections to neocortical excitatory cells; Nat Neurosci. 2011 Jan, 14(1): 100-107. doi: 10.1038/nn2687. PDF.

Mitarbeiter

NachnameVornameTitel             Tel.Fax.BüroLaborGeb.Funktion                                                    
KilonzoKasyokaM.Sc.33775337794544401-7N26PhD-Student Doktorand
KätzelDennisJun.-Prof. Dr.33770337794534401-7N26Gruppenleiter
KapanaiahSampathM. Sc.337753377944054401-7N26PhD-Student Doktorand
JendrykaMartinM. Sc.337753377944054401-7N26PhD-Student Doktorand
SchmidMarkB.Sc.337753377944054401-7N26Wiss. Hilfskraft
SchulzStefanie15248337794544401-7N26

Techn. Assistentin

Steele-PerkinsPeterB.Sc.337753377944054401-7N26

M.Sc.-Student
Wiss. Hilfskraft

van der VeenBastiaanM. Sc.33775337794544401-7N26PhD-Student Doktorand