Fos expression following regimens of predator stress versus footshock that differentially affect prepulse inhibition in rats

Abstract

Stress is suggested to exacerbate symptoms and contribute to relapse in patients with schizophrenia and several other psychiatric disorders. A prominent feature of many of these illnesses is an impaired ability to filter information through sensorimotor gating processes. Prepulse inhibition (PPI) is a functional measure of sensorimotor gating, and known to be deficient in schizophrenia and sometimes in post-traumatic stress disorder (PTSD), both of which are also sensitive to stress-induced symptom deterioration. We previously found that a psychological stressor (exposure to a ferret without physical contact), but not footshock, disrupted PPI in rats, suggesting that intense psychological stress/trauma may uniquely model stress-induced sensorimotor gating abnormalities. In the present experiment, we sought to recreate the conditions where we found this behavioral difference, and to explore possible underlying neural substrates. Rats were exposed acutely to ferret stress, footshock, or no stress (control). 90 minutes later, tissue was obtained for Fos immunohistochemistry to assess neuronal activation. Several brain regions (prelimbic, infralimbic, and cingulate cortices, the paraventricular hypothalamic nucleus, the paraventricular thalamic nucleus, and the lateral periaqueductal gray) were equally activated following exposure to either stressor. Interestingly, the medial amygdala and dorsomedial periaqueductal gray had nearly twice as much Fos activation in the ferret-exposed rats as in the footshock-exposed rats, suggesting that higher activation within these structures may contribute to the unique behavioral effects induced by predator stress. These results may have implications for understanding the neural substrates that could participate in sensorimotor gating abnormalities seen in several psychiatric disorders after psychogenic stress.

Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors

“…Similar to predator exposure, this study demonstrates that robust c-Fos expression occurs in amygdala subregions in response to EPM exposure. Specifically, EPM or ferret odor exposure both resulted in increased c-Fos expression in the MEA; however, in contrast, EPM exposure resulted in increased c-Fos expression in the BLA whereas predator odor exposure had previously been shown not to affect total c-Fos expression (Baisley et al, 2011; Butler et al, 2011). Neuron activation in response to EPM was seen in areas outside the amygdala, specifically the Cg, NAcC, and Cl, which expands upon and supports previous research in the area (Duncan et al, 1996).…”

“…However, the latter study differed from the present study in that animals received subcutaneous injection of saline prior to the test. The regions of interest in this study are also known to express c-Fos after other anxiogenic stimuli such as foot shock avoidance and air puff (Duncan et al, 1996), as well as predator odor (Baisley et al, 2011; Dielenberg et al, 2001; Janitzky et al, 2009). The reliable activation of these limbic areas by aversive stimuli supports their involvement in behavioral responses to emotional stimuli, although the activation of distinct neuronal populations is seen with different anxiogenic stressors.…”

“…Our lab and others have previously shown that the MEA displays increased expression of c-Fos following exposure to predator odor (Baisley et al, 2011; Butler et al, 2011; Dielenberg et al, 2001; Martinez et al, 2011). In the current study we further examine the phenotypic characteristics of the activated neurons in the MEA following exposure to predator ferret odor and the EPM test.…”

Animal models of anxiety disorders and stress

“…95 For example, in rats, a single cat exposure modifies the function of brain areas (such as the amygdala, prefrontal cortex, and hippocampus) that have been associated with the genesis of PTSD symptoms in humans. 99,100 In this model, the animals are exposed to a live cat or its odor for 5-30 min and, after 7 to 21 days, are exposed to an animal model of anxiety such as the EPM, fear conditioning, or startle-potentiated responses. 74,96,98 Psychological and physical stress models Essentially, these models induce stress by exposing the animals to psychological or physical challenges.…”

Exposure to an Alarm Pheromone Combined with Footshock Stress Enhances Responsivity of the Medial Amygdala-Hippocampus Circuit

“…Predator odor was shown to activate the dorsomedial periaqueductal gray and medial amygdala [53], whereas footshock induced broad activation in the amygdala, anterior hypothalamus, ventral hypothalamus, premamilar hypothalamus, lateral septum, dorsal periaqueductal gray, and ventral hippocampus [44]. These structures activate the amygdala, conferring an emotional meaning to any sensorial stimulus.…”