Role of contextual fear memory in development of Posttraumatic Stress Disorder (PTSD)-like symptoms in mice

Symptoms of PTSD lead to an assumption that both associative (conditioned fear) and non-associative (sensitisation) memory components play a crucial role in the development and maintenance of the disease. A new animal model of PTSD has been established in our group. A single electric shock is applied to C57BL/6N mice and 28 days later a conditioned response to contextual trauma reminders and a fear reaction to a neutral tone in a novel environment are measured, mimicking the level of associative and non-associative fear in a human disease (Siegmund & Wotjak, 2007). To investigate the involvement and the interdependency of the two memory branches in the development of PTSD we manipulated a formation and expression of the contextual fear in the mouse model and explored consequences on the fear response to a neutral tone. When employing a contextual extinction procedure we observed a parallel decrease in conditioned and non-associative fear, indicating either a presence of the one underlining mechanism (generalization of contextual fear) or an interaction between the two processes. We are currently studying (i) the presence of the fear reaction to a neutral tone in the absence of the contextual fear memory and (ii) the role of „context generalization“ as a putative mechanism of the fear reaction to a neutral tone by using an immediate shock deficit and a context pre-exposure paradigm respectively. Our results will lead to a better understanding of the PTSD pathogenesis.