Wired to Respond

January 22, 2019

Written by: Nitsan Goldstein

 

In the list of viral YouTube video compilations that most of us have seen, there is bound to be one of babies tasting lemons for the first time. It’s too cute to resist- the eyes shut tight, nose and mouth crumple together, maybe even a head shake to tie it all together. Aside from making us laugh, this phenomenon is quite remarkable. Kids have very similar physical responses to a taste that they have never experienced before. It’s an innate response to a sensory experience, meaning that it occurs without any prior learning. We are born with it. The evolutionary benefits of innate responses like these are clear. Babies are born innately drawn to sweetness so that they drink their mother’s milk, for example, but averse to bitter taste, presumably because many toxins are bitter. The fact that humans and animals are born with these responses suggests that the brain is wired to perceive and respond appropriately to these sensory cues and that no prior experience or learning is required. So what structures in the brain are important for innate responses to sensory cues? Here we will take a close look at a study that tried to answer these questions using mice as an animal model and the system these creatures use as their primary source of sensory input- the sense of smell.

 

Rodents rely heavily on their sense of smell to guide their behavior. A study done in 2014 by researchers at Columbia University attempted to uncover the region of the brain that is important in innate responses to both aversive (fear-promoting) and attractive odors1. By putting mice in an arena where one corner has certain smells and tracking their movements, they were able to see which odors are avoided, and which are preferred by mice. They found, not surprisingly, a substance found in fox urine called TMT was highly aversive, while a floral odor often used in perfumes called 2-phenylethanol (2-PE), was attractive.

 

Next, they wanted to find the region in the brain that is essential in producing the avoidance and attraction responses to these odors. The first area of the brain that processes smell is the olfactory bulb. The olfactory bulb is strongly connected with several other areas of the brain, meaning neurons in the olfactory bulb send dense projections to other regions that then communicate with neurons in those areas. Using a technique called optogenetics, the team was able to shut off communication between the olfactory bulb and each of these regions while testing their responses to the odors. They found that blocking communication between the olfactory bulb and a region called the cortical amygdala eliminated both avoidance to TMT and attraction to 2-PE.

 

How is the amygdala related to these responses? The amygdala is a region of the brain that is heavily involved in processing emotional information such as fear. For many years, neuroscientists have been studying the human amygdala (Movie 1) and its role in psychiatric conditions such as anxiety and post-traumatic stress syndrome (PTSD)2. Therefore, it is not too surprising the Columbia researchers narrowed down its involvement in innate avoidance of and attraction to odors. In fact, it’s possible that the amygdala is one many areas important for these behaviors, and disrupting any one of them would prevent the responses. What is surprising, however, is the next finding, which is that this activity in this small region of the amygdala, the cortical amygdala, is alone sufficient to cause these innate behavioral responses.

 

Movie 1. The amygdala in the human brain. Movie from BodyParts3D.

 

How were the researchers able to show this? They used a sophisticated technique that allowed them to selectively activate neurons that were previously involved in the response to TMT and 2-PE. Using genetic and viral tools, they were able to “tag” neurons in the cortical amygdala that were active during presentations of TMT or 2-PE. They then placed the mice in the same arena used to measure odor avoidance/preference. The difference in this experiment, however, is that this time the corners did not contain an odor. Instead, when the mice entered one corner, the researchers were able to activate the previously tagged neurons. Incredibly, when the group activated neurons that were tagged during previous presentation of TMT in one corner of the arena, mice avoided that corner. When they activated neurons that were tagged during the previous presentation of 2-PE, mice spent more time in that corner. This experiment showed that even in the absence of olfactory cues, the activity of these neurons is enough to elicit a behavioral response.

 

What can we learn about our own behavioral responses to sensory cues from studies like these? Importantly, how can this information help people whose brains’ alarm systems are overactive and experience anxiety disorders such as PTSD?  PTSD, while not an innate fear response, involves behavioral responses to sensory stimuli, like a sound, that has been associated with a traumatic event. As mentioned, rodent studies like the one described here have pinpointed the amygdala as a region important in the integration of sensory cues and the generation of behaviorally and physiologically relevant responses (such as the increased heart rate, sweaty palms, and pupil dilation associated with a fearful cue). In fact, studies using fMRI in PTSD patients found decreased connectivity between the amygdala and the cortex, the area of the brain that can override these subconscious fear responses elicited by sensory cues in PTSD patients3. Interestingly, patients undergoing cognitive behavioral therapy to treat PTSD showed increases in connectivity, suggesting that perhaps this type of therapy strengthens these connections3.

 

One of the brain’s most important jobs is to sense our environment and determine the appropriate behavioral response based on our needs, our previous experience, and the fears and the desires we are born with. Like a toddler scrunching his nose when he tastes a lemon for the first time, some of these behaviors are not learned. The cortical amygdala is essential for these innate behaviors, and insight into the neural circuits underlying these behaviors can narrow down targets for the treatment of anxiety disorders.

 

 

 

 

References:

  1. Root, C.M., Denny, C.A., Hen, R., & Axel, R. (2014). The participation of the cortical amygdala in innate, odour-driven behaviour. Nature 515, 269-273.
  2. Ressler, K.J. Amygdala Activity, Fear, and Anxiety: Modulation by Stress (2010). Biol Psychiatry 67, 1117-1119.
  3. Shou, H., et al. (2017). Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD. Neuroimage Clin. 14, 464-470.

 

Images:

Cover Image: by Roy17, Wikimedia Commons CC 1.0. https://commons.wikimedia.org/wiki/File:%E9%85%B8%E7%9A%84%E8%A1%A8%E6%83%85.jpg

Movie 1: Movie 1: Movie from BodyParts3D, © The Database Center for Life Science licensed under CC Attribution-Share Alike 2.1 Japan. https://commons.wikimedia.org/wiki/File:Amygdala_small.gif

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