Sex Differences in Hippocampal Immediate-Early Gene Expression following Context Fear Conditioning
Mentor 1
James Moyer
Start Date
1-5-2020 12:00 AM
Description
Women are twice as likely to suffer from posttraumatic stress disorder (PTSD) than males (Richards & Van Neil, 2017). PTSD can be modeled in the lab using Pavlovian fear conditioning. The paradigm used for this experiment is context fear conditioning, in which rodents learn to associate an environment with an aversive stimulus (foot shock). Some studies have shown sex differences in context fear learning (e.g., Maren et al., 1994). However, other work did not observe sex differences in short-term acquisition, instead observed sex differences in molecular mechanisms that may underlie differences in later retrieval of fear learning (Gresack et al., 2009). We used context fear conditioning in male and female rats to investigate how fear learning changes immediate early gene (IEG) expression. IEGs are activity markers that are evoked by environmental stimuli. We measured IEG expression in two brain regions that are important for context fear learning, the dorsal and ventral hippocampus. Context fear conditioning involves rats being placed in a conditioning chamber where they receive footshocks. Rats learn to associate the context with the footshocks, and this can be measured by freezing behavior. A day later, rats are placed in the same chamber but without footshocks and freezing behavior is measured. An hour later, their brains are removed and processed for protein analysis. Western blots are used to quantify the amount of IEG expression in the dorsal and ventral hippocampus. Initial behavioral results indicate that there are no sex differences in retrieval of context fear memories. Any observed sex differences in IEG expression in the hippocampi following memory retrieval, would suggest that the molecular mechanisms may differ between males and females even following comparable retrieval of context fear memories. Understanding sex differences in molecular mechanisms of fear learning may explain why females are more susceptible to PTSD.
Sex Differences in Hippocampal Immediate-Early Gene Expression following Context Fear Conditioning
Women are twice as likely to suffer from posttraumatic stress disorder (PTSD) than males (Richards & Van Neil, 2017). PTSD can be modeled in the lab using Pavlovian fear conditioning. The paradigm used for this experiment is context fear conditioning, in which rodents learn to associate an environment with an aversive stimulus (foot shock). Some studies have shown sex differences in context fear learning (e.g., Maren et al., 1994). However, other work did not observe sex differences in short-term acquisition, instead observed sex differences in molecular mechanisms that may underlie differences in later retrieval of fear learning (Gresack et al., 2009). We used context fear conditioning in male and female rats to investigate how fear learning changes immediate early gene (IEG) expression. IEGs are activity markers that are evoked by environmental stimuli. We measured IEG expression in two brain regions that are important for context fear learning, the dorsal and ventral hippocampus. Context fear conditioning involves rats being placed in a conditioning chamber where they receive footshocks. Rats learn to associate the context with the footshocks, and this can be measured by freezing behavior. A day later, rats are placed in the same chamber but without footshocks and freezing behavior is measured. An hour later, their brains are removed and processed for protein analysis. Western blots are used to quantify the amount of IEG expression in the dorsal and ventral hippocampus. Initial behavioral results indicate that there are no sex differences in retrieval of context fear memories. Any observed sex differences in IEG expression in the hippocampi following memory retrieval, would suggest that the molecular mechanisms may differ between males and females even following comparable retrieval of context fear memories. Understanding sex differences in molecular mechanisms of fear learning may explain why females are more susceptible to PTSD.
