Neuroscience Seminar - Stefan Herlitze, Ph.D.

May 1, 2018
9:00 AM - 10:00 AM
MJIS 1001


Stefan Herlitze, Ph.D.

Professor, Department of General Zoology and Neurobiology, Ruhr University Bochum, Germany

"Understanding and optogenetic control of signaling pathways involved in P/Q-type channel and serotonin receptor mediated diseases"

Our laboratory is interested in understanding diseases related to monoaminergic transmitters such as serotonin and to diseases related the P/Q-type Ca2+ channels.

Changes in serotonin levels in the brain are associated with various diseases including schizophrenia, obesity, anxiety disorders and depression. Therefore, understanding how serotonin modulates cortical activity and behavior and which signaling pathways are involved is an important contribution to understand the mechanisms of how these diseases originate. More importantly, we could recently show that controlling of 5HT2C receptor (Spoida et al. (2014) PNAS, 111, 6479-84) or 5HT1A (Masseck et al. (2014) Neuron, 81, 1263-73) receptor signals using light-activated GPCRs in different cell-types in the dorsal raphe nuclei, a brain region with high concentration of serotonin neurons, was sufficient to relieve anxiety in mice. We are currently developing new tools to control and monitor the activation of 5HT receptors in subcellular microdomains with G protein specificity in vivo.

P/Q-type channels are the prominent voltage gated Ca2+ channels in brain involved in synaptic transmitter release and action potential firing. Various diseases are associated with a reduction in function of the P/Q-type channel including ataxia, dyskinesia and absence epilepsy, but which neuronal cell-type contributes to the diseases and when during development these diseases originate is not known. In order to address these questions we developed a mouse model to cell-type specifically delete the channel in mice. Using these mice we could show that loss of the P/Q-type channel in cerebellar Purkinje and/or Granule cells after birth is sufficient to cause ataxia, absence epilepsy and stress-induced motor seizures (Mark et al. (2011) J. Neuroscience, 31(11):4311-26; Maejima et al. (2013) J. Neuroscience, 33(12):5162-74). The results suggest that alteration in the output of the cerebellar cortex is sufficient to cause and manifest the diseases. This is in particular surprising for absence epilepsy, which has been linked to changes in thalamo-cortical activity. In addition, we developed a mouse model for the human disease spinocerebellar ataxia type 6 (SCA6). These mice develop SCA6 like symptoms, i.e. deficits in motor learning, ataxia and PC degeneration. The physiological phenotypes can be explained by an impairment of LTD and LTP in the cerebellar cortex (Mark et al. (2015) J. Neuroscience, 35(23):8882-95). We are currently using the different mouse models in combination with optogenetic techniques to understand how the disease phenotypes originate during development, how stress is triggering the disease and if the disease phenotype can be stopped/converted by activation of specific signaling pathways in the cerebellar cortex.

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