1) Name – Title of the research project in CCHD
Thomas Klausberger – Molecular and cellular machineries in cortical networks
2) Coordinates of the Faculty Member
Center for Brain Research, Div. Cognitive Neurobiology, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. Email: thomas.klausberger@meduniwien.ac.at
3) Keywords
Hippocampus, prefrontal cortex, network oscillations, GABAergic interneurons, synaptic connectivity
4) Research interest of the Faculty Member
Dr. Klausberger is interested in spatio-temporal organisation of cortical networks in regard to network oscillations, memory formation, learning and decision making. In the recent past, he has investigated the contribution of identified GABAergic interneurons to theta, gamma and ripple oscillations in the hippocampus of anaesthetised rats; the temporal activity of distinct cell types was related to their synaptic connectivity and molecular expression profile. Recently, he has started to investigate the temporal and synaptic organisation in the medial prefrontal cortex of freely-moving rats performing working memory and decision making tasks. These studies are supplemented by a detailed immunohistochemical analysis of neurotransmitter receptors and transporters, neuropeptides and their receptors, voltage-gated ion channels and Ca2+ binding proteins in GABAergic interneurons of the medial prefrontal cortex.
5) Short description of two showcases of PhD Research Projects
Mr John Tukker has started his doctoral studies in October 2005 in the lab of Dr. Klausberger at the MRC Anatomical Neuropharmacology, University of Oxford supported by a studentship of the Medical Research Council covering his university and college fees as well as a personal allowance. At that time, John had a strong computational background but was short of practical experience in Neurobiology. Nevertheless, he quickly learned difficult in vivo recordings of identified interneurons in anaesthetised rats and the subsequent histological analysis of the recorded neurons with immuno-fluorescence and light microscopy as well as cell reconstructions. Using his computational and mathematical skills, he developed novel methods of analysing the in vivo recorded data with multiple correlations between single cell activity and network oscillations across different brain areas. His work has already resulted in a first-author publication (Tukker et al., 2007) and he is currently preparing a manuscript for another first-author paper. John has won several grants to support conference attendances including the British Neuroscience Association Travel Bursary, the FENS travel stipend as reimbursement for abstract editing and the Brasenose College, University of Oxford, Michael Woods Travel Grant and he presented his work in poster sessions at the “Neuronal Circuits: from Structure to Function” 2008 meeting in Cold Spring Harbor, USA; at the “From Molecules to Neuronal Circuits” 2007 meeting at the LMB, Cambridge, UK; and at the FENS2008 meeting in Geneva. John has submitted his DPhil thesis in February 2009 and he will start a postdoc position in the prestigious lab of Michael Brecht in Berlin in March 2009.
Miss Katja Hartwich has started her doctoral studies in August 2005 in the lab of Thomas Klausberger at the Center for Brain Research, Medical Univ. Vienna, Austria supported by a PhD position under the FWF grant P16637. Katja’s background was mainly in general biology and her diploma thesis engaged in behavioural neuroscience of bats. Nevertheless she quickly learnt the in vivo recordings of identified neurons, their specific labelling with the juxtacellular filling technique, subsequent immuno-fluorescence and light microscopic analysis of the cells, 3D reconstruction of filled dendrites and axons with Neurolucida and computational analysis of recording data. She made important contributions to a published paper on hippocampal interneurons in which she featured as a co-author (Tukker et al., 2007). However, her main focus was set on interneurons in the medial prefrontal cortex, which was a completely novel field in the lab of Thomas Klausberger. Katja achieved the first in vivo recordings of identified interneurons in this brain area and she has submitted her results as a first-author manuscript to the Journal of Neuroscience, which was positively reviewed and is currently under revision. Recently, Katja has won a place in the highly competitive PENS/HERTIE Winter School 2008/2009 “Structure and function of neuronal networks” in Obergurgl, where she presented a poster and learned and discussed scientific concepts with world-leading scientists. Also, Katja presented a poster at the International Neuroscience Winter conference in Soelden in 2008. Katja is currently preparing her PhD thesis, which she will submit in spring 2009. Because of her wide knowledge and experience in in vivo electrophysiology, immunohistology and computational data analysis she has been offered several post-doc positions, and Katja will continue her scientific career in academia.
6) Collaborations within CCHD
With W. Sieghart, there is a long-standing collaboration (7 joint publications) with respect to the molecular biology, pharmacology and localisation of GABAA receptors; this will be extended in CCHD. With S. Boehm and M. Freissmuth the cell type-specific expression of voltage-gated ion channels, presynaptic transmitter-gated channels, G-protein coupled receptors and neurotransmitter transporter will be investigated and the contribution of these channels to cortical network operations in vivo will be tested with pharmacological intervention. With H. Lassmann, there will be technical collaborations in immunohistochemistry and electron microscopy and intellectual interactions on how dysfunctions in spatio-temporal cortical networks result in pathological conditions.
7) Collaborating research groups where PhD Students can perform their research stay
Prof. William Wisden, Institute of Medical Sciences, University of Aberdeen, Scotland
Prof. Peter Somogyi, MRC Anatomical Neuropharmacology Unit, Oxford University, UK
Dr. Jozsef Csicsvari, MRC Anatomical Neuropharmacology Unit, Oxford University, UK
8) Know-how and infrastructure of the research group
This research group has demonstrated that different classes of GABAergic interneuron, distinguished by distinct synaptic connectivity and molecular expression profile, also make distinct contributions to neuronal timing of cortical networks in vivo (Klausberger et al., 2003; Klausberger and Somogyi, 2008); these spatio-temporal networks underlie the generation of different network oscillations and brain states. In addition, they discovered novel neuronal cell types in the hippocampus (Fuentealba et al., 2008; Jinno et al., 2007) and the cell-type specific localisation of signalling molecules (Baude et al., 2007; Klausberger et al., 2002).
This research group uses electrophysiological recordings in anaesthetised and freely-moving rodents using glass and/or tetrodes recordings. Juxtacellular filling of the recorded neurons allow their subsequent immunohistochemical analysis using immunoflourescence microscopy, electron microscopy and 3D reconstruction of dendrites and axons with Neurolucida light microscopy.
All major equipment required for the accomplishment of the CCHD research proposal will be present at the Center for Brain Research, including three in vivo electrophysiological recording set-ups (128 channel recordings of multiple cortical neurons and neuronal ensembles during the performance of cognitive tasks and two set-ups are designed for juxtacellular recordings with glass electrodes from identified cortical neurons in parallel with 32 channel multi-unit tetrode or silicon probe recordings), workshop facilities, light-, stereo- and immuno-fluorescence microscopes, a Neurolucida suite for the 3D reconstruction of neurons, and state-of-the art animal facilities. The Center for Brain Research also houses an electron microscope and two confocal fluorescence microscopes, which will be made available for the work on the CCHD proposal.
