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Expression of freezing and fear‐potentiated startle during sustained fear in mice
Authors:T Daldrup  J Remmes  J Lesting  S Gaburro  M Fendt  P Meuth  V Kloke  H‐C Pape  T Seidenbecher
Affiliation:1. Institute of Physiology I, Westf?lische Wilhelms‐University Münster, Münster;2. Institute for Pharmacology and Toxicology & Center for Behavioral Brain Sciences, Otto‐von‐Guericke‐University, Magdeburg;3. Department of Neurology and Institute of NeuropathophysiologyWestf?lische Wilhelms‐University Münster;4. Department of Behavioural Biology, Westf?lische Wilhelms‐University Münster, Münster, Germany
Abstract:Fear‐potentiated acoustic startle paradigms have been used to investigate phasic and sustained components of conditioned fear in rats and humans. This study describes a novel training protocol to assess phasic and sustained fear in freely behaving C57BL/6J mice, using freezing and/or fear‐potentiated startle as measures of fear, thereby, if needed, allowing in vivo application of various techniques, such as optogenetics, electrophysiology and pharmacological intervention, in freely behaving animals. An auditory Pavlovian fear conditioning paradigm, with pseudo‐randomized conditioned–unconditioned stimulus presentations at various durations, is combined with repetitive brief auditory white noise burst presentations during fear memory retrieval 24 h after fear conditioning. Major findings are that (1) a motion sensitive platform built on mechano‐electrical transducers enables measurement of startle responses in freely behaving mice, (2) absence or presence of startle stimuli during retrieval as well as unpredictability of a given threat determine phasic and sustained fear response profiles and (3) both freezing and startle responses indicate phasic and sustained components of behavioral fear, with sustained freezing reflecting unpredictability of conditioned stimulus (CS)/unconditioned stimulus (US) pairings. This paradigm and available genetically modified mouse lines will pave the way for investigation of the molecular and neural mechanisms relating to the transition from phasic to sustained fear.
Keywords:Anxiety  behavior  conditioning  fear  freely moving  learning  mouse  predictability  retrieval  unpredictability
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