AG Kätzel - N26

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 electro- and optophysiology, incl. multi-site LFP-recordings, miniscope-based imaging, and auditory endophenotyping
• behavioural analysis and behavioural pharmacology
• transgenic models of schizophrenia
• machine-learning based analysis

Public scientific resources provided by the Kätzel Lab:

• Suite of MATLAB Scripts for connectivity analysis of multi-site local field potential data
• Design files for open-source operant box optimized for electro- and optophysiology
• GUI and task-scripts for pyControl-based operant box experiments
• Multi-site LFP recording data during different behavioural tasks

Social Media

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Kapanaiah SKT, Kätzel D (2023): Open-MAC: A low-cost open-source motorized commutator for electro- and opto-physiological recordings in freely moving rodents. HardwareX, doi: https://doi.org/10.1016/j.ohx.2023.e00429

Kilonzo K, Strahnen D, Prex V, Gems J, van der Veen B, Murthy BKB, Kapanaiah S, Schulz S, Sprengel R, Bannerman DM, Kätzel D (2022): GluA1-containing AMPA receptors of distinct hippocampal subfields mediate salience processing, memory and impulse control. Translational Psychiatry, 12:102, doi: 10.1038/s41398-022-01863-8

Kapanaiah S, van der Veen B, Strahnen D, Akam T, Kätzel D (2021): A low-cost open-source 5-choice operant box system optimized for electrophysiology and optophysiology in mice. Scientific Reports 11:22279; doi: 10.1038/s41598-021-01717-1

van der Veen B, Kapanaiah S, Kilonzo K, Steele-Perkins P, Jendryka M, Schulz S, Tasic B, Yao Z, Zeng H, Akam T, Nicholson J, Liss B, Nissen W,  Pekcec A, Kätzel D (2021): Control of impulsivity by G_i-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex. Communications Biology 4:662; doi: 10.1038/s42003-021-02188-w

Kilonzo K, van der Veen B, Teutsch J, Schulz S, Kapanaiah SKT, Liss B, Kätzel D (2021): Delayed‑matching‑to‑position working memory in mice relies on NMDA‑receptors in prefrontal pyramidal cells. Scientific Reports 11:8788; doi: 10.1038/s41598-021-88200-z

Strahnen D, Kapanaiah SKT, Bygrave AM, Liss B, Bannermann DM, Akam T, Grewe BF, Johnson EL, Kätzel D (2021): Highly task-specific and distributed neural connectivity in working memory revealed by single-trial decoding in mice and humans. bioRXiv; doi: 10.1101/2021.04.20.440621

Strahnen D, Kapanaiah SKT, Bygrave AM, Kätzel D (2021): Lack of redundancy between electrophysiological measures of long-range neuronal communication. BMC Biology 19:24; doi: 10.1186/s12915-021-00950-4

Kätzel D, Wolff AR, Bygrave AM, Bannermann DM (2020): Hippocampal hyperactivity as a druggable circuit-Level origin of aberrant salience in schizophrenia. Frontiers Pharmacology 11:486811; doi: 10.3389/fphar.2020.486811

Bygrave AM, Kilonzo K, Kullmann DM, Bannermann DM, Kätzel D (2019): Can N-Methyl-D-aspartate receptor hypofunction in schizophrenia be localized to an individual cell type? Frontiers Psychiatry 10:835; doi: 10.3389/fpsyt.2019.00835

Teutsch J, Kätzel D (2019): Operant assessment of DMTP spatial working memory in mice. Frontiers Behavioural Neuroscience 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. Translational Psychiatry 9:142; doi: 10.1038/s41398-019-0471-0.

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

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. Frontiers Behavioural Neuroscience 12:332; 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. Scientific Reports 8:12871; 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. Frontiers Molecular Neuroscience 11:103; doi: 10.3389/fnmol.2018.00103

Kohl MM, Kätzel D (2017): Optogenetic mapping of neuronal connections and their plasticity, Book chapter in Appasani K (ed.): Optogenetics: from neuronal function to mapping and disease biology. Cambridge University Press; ISBN: 978-1-107-05301-4

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 6:778; doi: 10-1038/tp.2016.44

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 7:10584; doi: 10.1038/ncomms10584. 

Kätzel D, Kullmann D (2015): Optogenetic and chemogenetic tools for drug discovery in schizophrenia. Book chapter in: Lipina T, Roder J (eds.): Drug discovery for schizophrenia. RSC Publishing; 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 5:3847; doi: 10.1038/ncomms4847. 

Kätzel D, Miesenböck G (2014): Experience-dependent rewiring of specific inhibitory connections in adult neocortex. PLoS Biology 12:1001798; 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. Nature Neuroscience 14:100-107; doi: 10.1038/nn2687