Long-Term Changes in Spontaneous Behavior and c-Fos Expression in the Brain in Mice in the Resting State in a Model of Post-Traumatic Stress Disorder

The development of post-traumatic stress disorder (PTSD) in humans includes a number of symptoms, the main being intrusive memories of the trauma, psychological and physiological hyperreactivity on reminding of the trauma, and increased anxiety, and specific memory impairments. Current models of PTSD in animals address the last three of these symptoms but do not provide for study of spontaneously arising intrusive memories or their neural basis. The study reported here uses contemporary methods for continuous monitoring of behavior and showed that the development of PTSD in mice was accompanied by specific changes in spontaneous behavior in their home cages. These changes were long-lasting and included decreased exploratory activity and elevated anxiety. Thus, we showed that mice display the behavioral manifestations of human-typical spontaneously arising PTSD symptoms which in humans are associated with intrusive memories of the trauma. In addition, studies of neuron electrical activity-dependent expression of transcription factor c-Fos showed that the brains of mice with PTSD, even when the animal was at rest and not receiving external reminders of the trauma experienced, showed increased spontaneous activity in the cingulate and retrosplenial cortex, amygdala, thalamus, and periaqueductal gray matter. Thus, our studies demonstrated the spontaneous manifestations of PTSD in a mouse model at both the behavioral and neural levels.