Combining electrophysiology and behavioural tests to explore cellular and molecular mechanisms of behaviour and learning

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It is one of the major challenges for modern Neuroscience to find out how behaviour and behavioural plasticity is generated in the mammalian brain. We will combine in vitro electrophysiology with behavioural and pharmacological tests in vivo in order to explore cellular and molecular mechanisms underlying behaviour and learning. We use a well established simple model - the mammalian startle response - in order to be able to connect cellular events to behaviour. The startle response is mediated by a short and well described primary pathway, it can easily be quantified and it is modulated by sensory gating mechanisms, emotions and learning. One prominent intrinsic startle modulation is habituation to the repeated presentation of startle stimuli. Habituation is considered one of the most essential learning tasks and we all perform habituation learning throughout our daily life without noticing it.After refining the knowledge about the central pathway that mediates startle responses, we are now interested in cellular mechanisms of startle modulations. We were able to identify the cellular mechanism presumably underlying short-term habituation of startle responses in rodents: secondary sensory neurons within the primary startle pathway are subject to synaptic depression upon repeated activation. Based on this, the goal of our studies is to demonstrate that synaptic depression and habituation are closely realted. We further want to completely understand the molecular processes that lead to synaptic depression and eventually to habituation. In addition, we want to identify different neurotransmitter receptors and pathways that are able to interfere with the startle pathway and are therefore candidates to mediate sensory gating and emotional effects on startle. Our work will provide the first comprehensive description of a mammalian learning task and it will help to significantly advance the basic knowledge about how human and animal brains generate behaviour and behavioural plasticity.