Prof. Dr. Stefan Herlitze, Neurobiology, Faculty of Biology and Biotechnology
Research Programme:
My lab is interested in understanding ion channel function and system modulation in animal physiology and behavior. Our research is centered on the characterization of voltage gated Ca2+ channels and their modulatory proteins in cerebellum and hindbrain. We will apply patch clamp measurements in cultured cells and slice preparations, virus mediated infection methods (Sindbis virus), imaging techniques (two photon microscopy, TIRF, FLIM, FRET, FRAP, BiFC) and mouse genetics (transgene expression and homologous recombination) to investigate the following topics:
- Defining the role of P/Q-type Ca2+ channels domains for subcellular targeting, function and animal behavior. Ca2+ channels mediate voltage-dependent Ca2+ influx in subcellular compartments of neurons, triggering such diverse processes as neurotransmitter release, dendritic action potentials and excitation-transcription coupling. A fundamental question that remains unsolved is how Ca2+ channels are targeted to the appropriate cellular compartments especially the presynaptic terminal. This issue is critical to understanding both the basic physiology of neurons as well as several important neurological diseases such as familial hemiplegic migraine (FHM) and spinocerebellar ataxia 6 (SCA6), where mutations in voltage-gated Ca2+ channels cause changes in the density of Ca2+ channel complexes, alter their biophysical properties and change their potency to interact with intracellular modulating proteins like G proteins and Ca2+ channel ancillary subunits. We are in particular excited about investigating the role of the human P/Q-type SCA6 mutation in the living animal. The future goal of this research is to understand the mechanism of the disease process and to develop a cure.
- Defining the role of G protein modulation and neuronal activity of the serotonergic transmitter system for animal physiology (blood pressure regulation) and behavior (anxiety and depression). The vertebrate serotonergic neurotransmitter system consists of a relatively small number of neurons, which project to the spinal cord and into almost every brain region. This expansive projection system thereby permits serotonergic neurons to modulate important physiological and behavioral functions such as mood, sexual behavior, circadian rhythm and anxiety. We are in particular interested in understanding how the regulation of G protein modulation within the serotonergic system influences the signaling output in the brain. This will ultimately lead to the understanding of mammalian behavior and may accelerate the development of therapeutic treatments for anxiety and depression.