Though being afraid may not be a particularly enjoyable feeling, the ability to experience fear is actually pretty important, ensuring that animals react appropriately to dangerous situations. Understanding how fear responses are hardwired into the brains of different species provides a fascinating insight into how certain neural circuits have played a role in their survival, revealing key information about the importance of fear in the evolution of all complex life forms.
By way of example, mice are known to exhibit a stereotypical fear response to certain odors, such as that produced by bobcat urine and a fox odor known as TMT. Upon detecting these smells, mice usually freeze, with this response being generated by an increase in blood levels of stress hormones such as adrenocorticotropic hormone (ACTH) and corticosterone.
The secretion of these hormones is controlled by corticotropin-releasing hormone (CRH) neurons, which are found in a brain region called the hypothalamus. These neurons receive signals from multiple areas of the olfactory cortex (OC) – the part of the brain that processes smells – although little is known about which specific areas of the (OC) control the stress hormone response to predator odors.
To investigate this, researchers from the Howard Hughes Medical Institute injected mice with certain neural activity markers, and investigated how neurons in the OC responded to the presence of bobcat urine and TMT.
Publishing their results in the journal Nature, the study authors reveal how CRH neurons in a tiny area known as the amygdalo-piriform transition area (AmPir) – which makes up less than 5 percent of the OC – appeared to modulate the fear response to these odors. Activity within the AmPir increased almost six-fold in the presence of TMT, and five-fold when bobcat urine was detected.
To confirm the role of the AmPir in this fear response, the researchers used a process known as chemogenetics to artificially stimulate this region of the mice’s olfactory cortex with no predator odors present, and found that this caused blood levels of ACTH to increase by 7.6 times.
They then used the same technique to silence the AmPir, and found that the expected rises in stress hormone levels when mice were exposed to predator odors did not occur. As such, they conclude that the AmPir plays a pivotal role in the hormonal fear response to predator odors.
Interestingly, this neural circuit appears to be inherited rather than learned, as even those mice that had never been exposed to bobcat urine or TMT in the wild – and therefore knew not of the dangers posed by these predators – experienced the same increase in stress hormone levels when encountering these odors, leading to the stereotypical freezing response.
Equally fascinating is the fact that freezing still occurred even when the AmPir was silenced, suggesting that the hormonal and behavioral fear responses to predator odors are regulated by different parts of the brain.