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(Neuro)biological Techniques

Part of our research questions is to examine  various behaviors on a neurobiological level. In psychiatric and neurodevelopmental disorders, mechanisms in the brain or the genetic composition can affect behavior in many ways. Genetic mutations or alterations in synaptic transmission, neurotransmitter and protein levels can lead to behavioral differences.

On the cellular level, single neurons or neuronal bundles and their activity can be recorded or neurons in specific target brain regions can be stimulated to evoke different behavioral outcomes.
To visualize distinct neurons - that are involved in specific behaviors - for further microscopic investigation, one can stain these cells via a technique called immunohistochemistry.

Alterations of specific proteins or neurotransmitters can be analyzed by assays like Western Blot or high-performance liquid chromatography (HPLC).

To test whether the genetic compositions of animal differ from each other, e.g. in genetic animal models for different neuropsychiatric disorders, genotyping is performed.

  • Deep Brain Stimulation

    Remote controlling our brain via electrical stimulation - Robot-Frankenstein come true ??

    We can´t control the whole brain (yet) by applying electrical current to it but we can still see that electrical stimulation has an effect on neuronal activity and behavior. DBS treatment in parkinsonian patients e.g. in the subthalamic nucleus or globus pallidus, ameliorates motor impairments. Since patients often suffer from side effects after DBS in these regions, we try to find alternative targets in parkinsonian rats. We implant electrodes into the rat brain and analyze the correspondence between DBS and the behavioral outcome in freely-moving rats.

  • Electrical Recording

    Are you sure… is there electricity in our brain?

    Yes, we are. Electrical signals can be detected by thin electrodes implanted into the brain areas of interest. Recording electrical signals is one way to answer questions like how do neurons interact, when and how frequently do they fire. In our lab we record neuronal activity in freely moving rats and draw conclusions on how brain areas work, interact and on their relations with certain behaviors.

  • ELISA

    ELISA (enzyme-linked immunosorbent assay) is a widely used immunoassay, allowing rapid screening and quantification of antigens (proteins) in the samples on a microplate. As in other techniques that identify and quantify specific proteins, antibody-antigen reaction is the basis of ELISA. Using antibodies linked to an enzyme and their substrates, a reaction that forms a colored product is catalyzed. Concentration of the protein of interest in the sample is then quantified by means of color intensity.

  • Genotyping

    Genotyping of animal models is a crucial routine in our lab that allows us identify genetic differences between animals, hence relate these to their behavior. Once the DNA is extracted from a sample, using assays such as PCR (polymerase chain reaction) we can make copies of gene of interest (e.g. SHANK1) and tell whether an animal has a mutation or not by visualizing these.

  • HPLC

    Depletion of dopamine leads to the symptoms of Parkinson’s disease. The high-performance liquid chromatography (HPLC) is a technique we use to determine the presence and the quantity of certain substance levels in different brain areas. For example, the dopamine system not only plays a crucial role in Parkinson’s disease but also in sign- and goal tracking behavior. Therefore, determination of dopamine and other molecules in biological samples provides an important key to understand the neurochemistry leading to a certain disease/behavior.

  • Immunohistochemistry

    Immunohistochemistry is a microscope-based technique for visualizing cells, e.g. new-born neurons, with specific markers in biological specimens.

    Neurogenesis is the process by which neuronal cells are formed in the brain. Hippocampus, in particular, holds a niche where new-born neurons can be found in adult human and rodent brains. These neurons play an important role in processes such as, memory and mood regulation. Several neuropsychiatric diseases, like depression or anxiety, have been linked to altered adult hippocampal neurogenesis.

    In rodents, it has been shown that the rate of adult hippocampal neurogenesis can be influenced by environmental changes, drugs or genetic background (e.g. Cacna1c).

    We use immunohistochemistry to mark new-born neurons in the hippocampus of rats which can be visualized by a microscope

     

    Literature

    Brenes JC, Lackinger M, Höglinger GU, Schratt G, Schwarting RKW, Wöhr M (2016) Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J Comp Neurol 524:1586–1607.

    Wöhr M, Kehl M, Borta A, Schänzer A, Schwarting RKW, Höglinger GU (2009) New insights into the relationship of neurogenesis and affect: Tickling induces hippocampal cell proliferation in rats emitting appetitive 50-khz ultrasonic vocalizations. Neuroscience 163:1024–1030.

  • Stereotactic Surgery

    For some investigation it is necessary to directly manipulate a specific brain area e.g. by administering drugs or causing lesions in order to assess its consequences. But how does one precisely locate the brain area of interest? This can be done by stereotactic surgery, a technique which allows us to target specific brain structures based on a set of references, such as bone landmarks. We use this technique in order to (i) implant guide cannulas that allow injection of drugs; (ii) induces specific lesions in the brain; (iii) insert electrodes to stimulate specific brain areas (Deep Brain Stimulation) or recording the neural activity (electrical recording).

  • Western Blotting

    Western blotting, also called immunoblotting, is a routine technique used to analyse individual proteins in a protein mixture (e.g. cell lysate). This method allows measuring certain molecules and the amount of them. We use it to investigate changes in protein expression in the brain corresponding to certain behavior of rats (e.g. Sign- and Goal-Tracking), as well as between different rat models (e.g. Cacna1c/ SERT).