Abstract WP239: Sexually Dimorphic Amygdala Dysfunction In A Mouse Model Of Global Ischemia

Abstract

Introduction: Advances in modern medicine have greatly increased chances of survival following traumatic events such as cardiac arrest, stroke, or heart attack. With more people able to recover from these ischemic insults, it is becoming apparent that survivors experience long-term effects as it relates to brain function. Despite clinical and animal model evidence of emotional dysfunctions following global ischemia, no study has attempted to identify amygdala dysfunction after Cardiac Arrest and subsequent Cardiopulmonary Resuscitation (CA/CPR). Utilizing a mouse model of CA/CPR-induced global ischemia, we have identified amygdala dysfunctions that are dependent on biological sex. We hypothesize that global ischemia results in deficits in amygdala-dependent learning tasks and circuit specific deficits of LTP in the basolateral amygdala (BLA). Methods: Seven days post CA-induced global ischemia, male and female adult C57BL/6 mice underwent amygdala dependent delay fear conditioning. In a separate cohort of animals acute-transverse slices were prepared seven days post global ischemia and extracellular field potential recordings were collected from the BLA. Results: We have revealed a sexually dimorphic deficit in amygdala dependent fear learning and memory. Both male and female mice display a previously reported contextual fear deficit (Male: 78.6 ± 2.6% sham freezing vs. 51.2±8.7% CA/CPR freezing, n=7; Female 70±5.1% sham freezing vs. 50.2±8.5% CA/CPR freezing, n=9), however, only male mice display a diminished freezing response to cued fear (56.4 ± 7.2% sham freezing vs. 31 ± 6.7% in CA/CPR, n=7). Similarly, plasticity involving cortical inputs to the basolateral amygdala is also disrupted in a sexually dimorphic manner, with only males displaying diminished LTP relative to sham controls (153.4 ± 8.1% of BL in controls, n=4 vs. 102.4 ± 3% of BL in CA/CPR, n=7). Conclusion: These results support the role of the amygdala in cognitive-affective impairments after CA-induced global ischemia and provide new insights into the role that biological sex plays in mediating brain dysfunction following CA. In the future, we will continue to unravel the mechanisms by which this sexually dimorphic impairment occurs and identify therapeutic targets.