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Free keywords:
startle response,fear conditioning,extinction learning,Ultramicroscopy,stimulus parameter
Abstract:
In neuroscience major efforts are focused on the question of how the mammalian brain generates and controls behaviour. The startle response is a relatively simple behaviour that can be easily elicited in mammals and is sensitive to a variety of experimental treatments.
The aim of the present work was to establish startle response measures at the Max-Planck-Institute of Psychiatry (MPI-P), Munich, providing a set of readily applicable methods and paradigms, and contributing to questions in behavioural neuroscience.
While the present thesis failed to robustly elicit fear potentiated startle (FPS) in a commonly used mouse strain at the MPI-P, strong unconditioned startle enhancement by acoustic stimulus presentation in that mouse strain was capitalised to propose tone enhanced startle (TES) as an additional paradigm to assess hearing capability, stimulus adaptation and attention in mice.
A literature survey revealed considerably varying parameters used in fear conditioning (FC) and extinction of conditioned fear (ExFC). In the present work, FC, ExFC as well as FPS/TES highly depended on the stimulus quality (i.e. sine wave or white noise), demanding a more careful handling of stimulus parameters.
Hyper-arousal was readily tested in a mouse model of posttraumatic stress disorder (PTSD). Additionally it was shown that altered hippocampal volume in these animals, assessed by ultramicroscopic measures and mimicking patient data, was independent of other symptoms present in this model.
The present thesis contributes to the ongoing characterisation of the role of dopamine receptors (DR) in prepulse inhibition (PPI) and prepulse facilitation (PPF) of startle, manipulating PPI/F by injections of DR-antagonists into the prefrontal cortex of mice.
It was found that blockade of DR1 reliably increases PPI, while the effect of DR2 was inconsistent, using to different DR2-antagonists. Based on this work, optogenetic methods were established. Applying intracerebral light flashes to transgenic mice carrying light sensitive ion channels on their neuronal cell membrane, PPI and PPF were manipulated independently, proposing the existence of a discrete PPF mediating pathway including prefrontal layer V pyramidal neurons, contrasting the popular summation hypothesis of PPF.
The present work established and developed successfully different startle paradigms that are ready to use for animal characterisation and testing. Apart from combining startle measures with new techniques such as optogenetic methods, the present thesis points out the stimulus parameter dependence of animal learning, suggesting a fundamental discussion about fear conditioning and extinction learning protocols.
