Over the years, neurological studies have increasingly pointed toward differences between the male and female brain, but neuroscientists are still exploring what, exactly, drives those sex-based differences. Now, a recent study published in Nature Neuroscience has revealed significant differences in how male and female mice process threats, even as they exhibit similar behavioral responses to those threats. Read on for more information about the implications of the mouse study, which involved recording neural activity in two nucleus accumbens (NAc) glutamatergic afferents during threatening and neutral cues.
Does Sex Influence Threat Perception? Mouse Study Says Yes
To evaluate how male and female mice perceive threats, the researchers studied two related brain circuits and their roles in processing information. The researchers hoped to gather information about threat responses, as well as the neurological cues that cause protective reactions to potential threats.
First, the researchers trained the mice to recognize a sound that signaled a threat. They then trained the mice to recognize another sound, which signaled safety. By observing the unique brain activity of the male and female mouse subjects, the team saw how communication between different brain areas processed these signals. Later, the researchers temporarily “turned off” each brain connection. The researchers were then able to analyze how each mouse’s brain perceived threats.
Understanding Sex-Based Threat Encoding
Before the study, scientists generally assumed that similar behavior pointed to similar brain function. For example, if two mice ran away from a perceived threat, it was assumed that the mice had similar brain functions driving them to attempt to escape. However, the study revealed sex-biased encoding of threat cue discrimination, even as the mice responded similarly to threatening situations. “We found that even though male and female mice respond similarly to threats, the brain circuits underlying these responses are not the same,” noted Rosemary Bagot, a McGill University Associate Professor, who led the study. For female mice, a connection between two specific brain areas — the medial prefrontal cortex and the nucleus accumbens — played an important role in processing threat cues. In male mice, however, the ventral hippocampus communicated with the nucleus accumbens during threat perception.
Moving forward, the research team behind the mouse study will continue exploring how biological sex impacts brain circuits while processing threats. This research will primarily focus on sex hormones. These discoveries may help promote more sex diversity in neuroscience research, driving researchers to work with both male and female subjects on a more regular basis. The findings could also lead to precision treatment options targeted toward a subject’s biological sex and the neurological implications of that factor. Finally, the findings could influence the medical community’s understanding of anxiety-related psychiatric diseases, as learning to predict a threat signal compared to the absence of a threat signal might influence disease development.
“Unless we thoughtfully and rigorously integrate sex into biomedical research, a huge amount of the population may be underserved by scientific knowledge,” said McGill University Associate Professor and Canada Research Chair in Behavioral Neurogenomics Rosemary Bagot, who led the study. “Our work shows that sex is an important variable to consider, even if initial observations don’t necessarily show clear sex differences. If males and females are using different brain circuits to solve similar problems, they may be differently vulnerable to stress and respond differently to treatments.”
To evaluate threat learning in rodents, Scantox Neuro offers the contextual fear conditioning and passive avoidance test. To evaluate anxiety-related behavior, we can apply the elevated plus maze test. All tests are readily available, and we have established several protocols to analyze different aspects of threat learning and anxiety.
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