Prof. Dr. Jörg Geiger

Geiger group

Physiology and Pathophysiology of cortical interneurons,
axons and presynaptic Boutons

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Research focus

The research group Geiger is engaged in the following science topics:

  • Molecular physiology, plasticity and synaptic function and dysfunction of interneuron subtypes in cortical networks

  • Network alterations and behavioural symptoms generated by interneuron dysfunction in animal models

  • Coding principles and energy efficiency of electrical signaling in cortical axons

Methods

The following methods are applied:

  • Somatic and presynaptic patch-clamp recordings in acute slices of rodent brain
  • Paired recordings from synaptically coupled neurons
  • Quantitative single-cell RT-qPCR after electrophysiological characterization
  • Adeno-associated virus mediated alterations of neuronal expression patterns in the rodent brain
  • Laser-capture microdissection and transcriptome analyses of immunohistochemically identified neurons
  • Animal models of psychiatric disorders: Correlation analysis between behavioural phenotype, molecular deviations and electrophysiological alterations of neurons and synaptic transmission (future project)

Paired recordings from synaptically coupled neurons: Oktapatch

Exemplary graph of the "connectome" of 8 simultaneously recorded neurons in the cortex. Foto: YP/Charité

The generation and propagation of neuronal population activity relies heavily on local network interactions, such as synaptic connectivity and plasticity. To investigate the micro-scale connectomics between individual cells, we established several in-vitro multi-neuron patch-clamp setups allowing visually guided recordings of up to 10 neurons simultaneously. Beyond highly efficient screening of unidirectional connections between specific cell types, this method also allows investigations of high-dimensional connectivity patterns (network motifs) and graph theoretical properties, such as degree distribution and hub-neurons. Using transgenic labelling and electrophysiological discrimination analysis, we also focus on interneuron subclasses to study their plasticity and connectivity profiles.

View onto the 10fold patch-clamp recording setup, the dekapatch. Foto: YP/Charité

Laser-capture microdissection and transcriptome analyses of immunohistochemically identified neurons

Digital Droplet analysis setup QX200. Foto: JT/Charité
Graphical fluorescence representation of a twofold multiplexed PCR reaction of single cells, detecting up tp 8 gene targetes per individual cell. Foto: JT/Charité

A further molecular biological method aims to investigate the internaluronal composition of hippocampal subregions at the single-cell level. By immunohistochemical fluorescence staining followed by laser dissection microscopy, interneurons in mouse and rat ultrathin sections are identified and isolated. Alternatively, the prepared hippocampi of transgenic animals, such as the YFP-Vgat rat, can be dissociated and the desired interneurons selected by fluorescence activated cell sorting (FACS) from the cell suspension.
The characterization of interneurons is achieved by analyzing selected transcripts via digital droplet PCR. Unlike a conventional qPCR, the reaction mixture is subdivided into up to 20,000 compartments and an endpoint measurement of fluorescence is performed. As a result, relative statements about the amount of transcript are not inferred on the basis of CT values, but the absolute transcript content of the cell is directly counted and adjusted according to Poisson statistics.
Thus, the gene composition of singel cells obtained allows the designation of interneurons subtypes and the expected electrophysiological characteristics of the cell an be inferred.

Funding

  • DFG Clinical Research Unit 247
         "Deep brain stimulation. Mechanisms of action, Cortex-Basal Ganglia-Physiology and Therapy Optimization."
    project 11(together with Christoph van Riesen)
         “Mechanisms of pathological oscillations in the cortico-basal ganglia loop and its modulation by deep brain stimulation in the 6-OHDA rat model of Parkinson´s disease.”
  • DFG Research Unit FOR 2143
         “Interneuron Plasticity – From Mechanisms to Higher Brain Functions”
    project 2 Jörg Geiger
         „Control of synchrony in fast network oscillations by synaptic plasticity in interneurons of M1“
  • Neurocure

Head of the institute

Univ.-Prof. Dr. rer.nat Jörg R. P. Geiger

Executive Director, Group leader

CCM: Campus Charité Mitte

Prof. Dr. Jörg Geiger
Univ.-Prof. Dr. Christian Rosenmund

vice director; project leader

CCM: Campus Charité Mitte

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Students and Alumni

MD/PhD students

Michael Hadler
Franz Mittermaier
Veronica Rignall
Leon Amadeus Steiner
John Thiede
Vera Wuntke

Alumni

PD Dr. Doris Albrecht

Dr. Constantin Klisch

Dr. Benjamin Marquez-Klaka

Dr. Stefanie Schinkel

Kerstin Rückwardt

Prof. Tengis Gloveli

Dr. Tamar Dugladze

Dr. Peter Bäuerle