Molecular Mechanisms underlying Habituation in the Startle Reflex of Mammals

• Applicant: Dr. Marei Typlt
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 206649272

Habituation is considered to be the most basic form of non-associative learning. It describes the decrease of behavioural response to repeated non-threatening sensory stimulation and therefore provides an important sensory filtering mechanism. Habituation is impaired in patients suffering from e.g. schizophrenia or autism spectrum disorders, which leads to information overload in higher brain areas causing cognitive deficits. While habituation is well studied behaviourally only little is known of the underlying molecular mechanisms. Based on a recent discovery of an evolutionary highly conserved fundamental habituation mechanism, I will investigate the molecular mechanisms underlying habituation of mammals. I will use habituation of the startle response in rats and transgenic mice as a model. This allows me to combine behavioural experiments with a well-established in vitro brain slice model for electrophysiological single cell recordings. In the proposed project I will focus on the high voltage- and calcium-activated, large-conductance potassium channel (BK-channel) that seems to be a key player in the conserved habituation mechanism. I will test the hypothesis that activation of BK channels is responsible for short-term habituation of the startle response in mammals and investigate the underlying mechanisms. Further, I will explore whether habituation can be enhanced by respective BK channel modulators. These experiments will not only give valuable insights into the mechanisms underlying non-associative learning but will help to identify potential drugs for a treatment of habituation deficits in patients. The pharmacological improvement of this early stage information processing will benefit cognitive functions in patients suffering from diseases involving habituation deficits, such as schizophrenia and autism spectrum disorders.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professorin Dr. Susanne Schmid