Anxiety, fear, panic: An approach to assessing the defensive behavior system across the predatory imminence continuum.

In order to effectively thwart predation, antipredator defensive behaviors must be matched to the current spatio-temporal relationship to the predator. We have proposed a model where different defensive responses are organized along a predatory imminence continuum (PIC). The PIC is a behavior system organized as a sequence of innately programmed behavioral modes, each representing a different interaction with the predator or threat. Ranging from low threat to predator contact, the PIC categorizes defense modes as pre-encounter, post-encounter, and circa-strike, corresponding to states of anxiety, fear, and panic, respectively. This experiment examined if the same significant stressor caused overexpression of all defensive responses along the PIC, including anxiety-like behavior, freezing, and panic-like responses. Female and male mice were exposed to acute stress that consisted of a series of ten pseudorandomly presented unsignaled footshocks (or no shocks). Mice were subsequently tested on a battery of tasks to assess stress effects on pre-encounter (anxiety-like), post-encounter (fear), and circa-strike (panic-like) behaviors. Results revealed that following stress, mice exhibited increased anxiety-like behavior shown through reduced average velocity within a modified open field. Furthermore, stressed mice showed increased fear following a single footshock in a new context as well as an increase in reactivity to white noise in the original stress context, with stressed mice exhibiting a more robust circa-strike-like response than controls. Therefore, significant stress exposure influenced the defensive states of anxiety, fear, and panic across the predatory imminence continuum. This research could therefore reveal how such responses become maladaptive following traumatic stress in humans.

Sex Differences in Behavioral Sensitivities After Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with high rates of post-injury psychiatric and neurological comorbidities. TBI is more common in males than females despite females reporting more symptoms and longer recovery following TBI and concussion. Both pain and mental health conditions like anxiety and post-traumatic stress disorder (PTSD) are more common in women in the general population, however the dimorphic comorbidity in the TBI population is not well-understood. TBI may predispose the development of maladaptive anxiety or PTSD following a traumatic stressor, and the impact of sex on this interaction has not been investigated. We have shown that white noise is noxious to male rats following fluid percussion injury (FPI) and increases fear learning when used in auditory fear conditioning, but it is unclear whether females exhibit a similar phenotype. Adult female and male rats received either lateral FPI or sham surgery and 48 h later received behavioral training. We first investigated sex differences in response to 75 dB white noise followed by white noise-signaled fear conditioning. FPI groups exhibited defensive behavior to the white noise, which was significantly more robust in females, suggesting FPI increased auditory sensitivity. In another experiment, we asked how FPI affects contextual fear learning in females and males following unsignaled footshocks of either strong (0.9 mA) or weaker (0.5 mA) intensity. We saw that FPI led to rapid acquisition of contextual fear compared to sham. A consistent pattern of increased contextual fear after TBI was apparent in both sexes across experiments under differing conditioning protocols. Using a light gradient open field task we found that FPI females showed a defensive photophobia response to light, a novel finding supporting TBI enhanced sensory sensitivity across modalities in females. General behavioral differences among our measures were observed between sexes and discussed with respect to interpretations of TBI effects for each sex. Together our data support enhanced fear following a traumatic stressor after TBI in both sexes, where females show greater sensitivity to sensory stimuli across multiple modalities. These data demonstrate sex differences in emergent defensive phenotypes following TBI that may contribute to comorbid PTSD, anxiety, and other neurological comorbidities.