Increased Heart-Rate Leads to Increased Anxiety-Like Behavior in Mice
Post by Lani Cupo
The takeaway
The authors find evidence that emotional states emerge not only top-down, with the brain influencing the body, but also in a bottom-up fashion, with changes to the body (increased heart-rate) increasing anxiety-like behavior.
What's the science?
In acting, there are two techniques to embody a character and scene: a popular inside-out approach where the actor uses a variety of approaches to feel an emotion internally and then expresses that internal state, and an outside-in approach where actors mold the voice and body to capture the emotion and allow it to influence their internal feelings. However, to what degree the physiological state, such as heart and breathing rate, can contribute to the development of an emotional state (like anxiety) is still debated scientifically. This week in Nature, Hsueh and colleagues found that experimentally controlling the heart rate of mice increased anxiety-like behavior, identifying the brain structures involved in the effect.
How did they do it?
First, the authors used cutting-edge genetic engineering to develop a mouse whose heart-rate they could control with a laser mounted on a vest and directed towards the chest (towards the heart, but over the skin). By pulsing the light, the authors could stimulate a heart-rate up to 900 beats per minute, although they could not slow the heart-rate below baseline rates. Mimicking patterns of increased heart-rate observed during stressful contexts, the authors examined the behavior of these “paced” mice compared to controls in two different anxiety tests. They also included an operant test, which examined reward-seeking in a stressful context—during mild foot shocks of variable frequencies.
Next, the authors used an ex-vivo assessment (CLARITY and cell-staining for neural activation) to examine what brain regions might be involved mechanistically in the observed effect. To confirm the role of the identified brain regions in cardiac pacing, they recorded activity from neurons in this region in live mice while increasing the heart rate. Finally, the authors investigated whether inhibiting activity in this brain region inhibited the anxiety-like behaviors observed during increased heart-rate.
What did they find?
The authors observed increased anxiety-like behavior in paced mice compared to controls on both the open-field test and the elevated-plus maze. Importantly, there were no baseline differences between mobility or anxiety levels, suggesting the differences were due to the increased heart-rate rather than the experimental manipulations. In the operant test, there were also no baseline differences in reward-seeking behavior of the experimental mice, however when mild foot shocks were delivered with the reward in 10% of trials, the experimental mice had suppressed reward-seeking. This indicates an apprehensive behavior, where the risk of a foot shock decreases the mouse’s reward-seeking behavior.
Next, the authors identified the posterior insular cortex (pIC) as a region of interest - a brain region known to play a role in interoception. These results were further supported by the authors’ findings that neurons in the pIC were more active when the heart-rate was increased.
Finally, the authors found that inhibiting activation in the pIC reversed the effects of the increased heart-rate in reward-seeking. That is, mice with increased heart-rates but also inhibited pICs no longer differed from controls in their reward-seeking behavior, even with the risk of a foot shock. The authors also tested whether inhibition of another brain region (medial prefrontal cortex) or pIC inhibition without increased heart-rate decreased anxiety-like behavior, and found that they did not. This provides very strong evidence that the pIC is crucially involved in the connection between increased heart-rate and an anxious state.
What's the impact?
This study presents strong evidence that increased heart-rate can evoke anxious states, and that the pIC is integral in this relationship. The methods used in this research add new techniques to the neuroscientist’s tool box, and these findings can help to pave the way for effective interventions for those suffering from panic and anxiety disorders.