Meek no more: turning mice into predators

A recent study published in the journal Cell, has shown that  switching on a particular group of neurons in the mouse brain can turn these otherwise timid creatures into aggressive predators. Why would anyone want to do this you might ask? After all, with the tumultuous political events of 2016, do we really want to add killer mice to our worries? Thankfully, the researchers aren’t planning to take over the world one rodent at a time, instead they want to understand how the brain coordinates the complex motor patterns associated with hunting.

During the evolution of vertebrates, the morphology of the head changed to allow for an articulated jaw. This is a more scientific way of describing the type of jaw most of us are familiar with: an opposable bone at the entrance of the mouth that can be used to grasp and manipulate food. This anatomical change allowed for the development of active hunting strategies and the associated neural networks to coordinate such behaviours. The researchers wanted to identify which parts of the brain contain the networks for critical hunting behaviours such as prey pursuit and biting. They began by looking at an evolutionarily old part of the brain known as the amygdala, specifically the central nucleus of the amygdala (CeA), because this area has been shown to increase its activity during hunting and has connections to parts of the brainstem controlling the head and face.

In order to study this part of the brain, the authors used a technique called optogenetics. This technique involves introducing the gene for a light sensitive ion channel into specific neurons. It is then possible  to ‘switch on’ the neurons (i.e. cause them to fire bursts of electrical activity) simply by shining blue light onto them. This is what the researchers did with the neurons in the CeA.

To begin with the researchers wanted to find out what happens when you simply switch on the these neurons. To test this they put small moving toys, resembling crickets, into the cage as ‘artificial prey’ and watched the animals’ behaviour. The mice were largely indifferent to these non-edible ‘prey’, however as soon as the light was switched on the mice adopted a characteristic hunting position, seized the toys, and bit them. This never occurred when light was off. The scientists also tested the mice with live crickets (i.e. prey that mice would naturally hunt). When using live prey the mice (without the light activation) hunted as normal. However, when the light was switched on the researcher saw that the time needed for the mice to capture and subdue their prey was much shorter and any captured crickets were immediately eaten. The combination of these results suggests that stimulation of the central nucleus of the amygdala (CeA) not only mimicked natural hunting but increased the predatory behaviour of these mice.

One question that might spring to mind from this study is: How do we know that these mice are really hunting? Perhaps the light had unintended effects such as making the mice particularly aggressive or maybe very hungry? After all, both explanations could account for the increased biting of non-edible objects and the faster, more aggressive cricket hunting. To argue against increased aggression levels, the authors point out that CeA stimulation did not provoke more attacks on other mice – something you might expect of an overly aggressive mouse. So what about increased hunger? The scientists in this study also think this is unlikely because they allowed the mice access to food pellets and found no difference in how many pellets were consuming during the time the laser was on versus the time the laser was off.

So how is hunting behaviour controlled by the CeA? The hunting behaviour displayed by mice can be divided into two aspects: locomotion (prey pursuit and capture) and the coordination of craniofacial muscles for the delivery of a killing bite. The scientists hypothesised that the CeA may mediate these two different types of behaviour through connections with different parts of the brain. The two key brain regions investigated in this study were the parvocellular region of the reticular formation in the brainstem (PCRt) and a region of the midbrain called the periaqueductal grey (PAG).

By using optogenetics the researchers were able to selectively stimulate the CeA to PCRt projection and found that this caused the mice to display feeding behaviours. Interestingly, stimulating this pathway seemed to only elicit the motor aspects of eating e.g. chewing rather than increasing the mice’s hunger. Conversely, disrupting the function of this pathway interfered with the mice’s ability to eat. Taking this into a ‘live’ setting, the mice could still pursue their prey and subdue it using their forepaws, but they struggled to deliver a killing bite. The researchers then turned their attention to the pathway between the CeA and the PAG. They found that stimulating this projection caused mice to start hunting more quickly, pursue their prey faster, and hunt for longer. Unlike the experiment above, stimulating this pathway had no effect on feeding-type behaviours. Now the scientists geared up for the big experiment: they’ve shown that stimulating the CeA leads to predatory hunting. They’ve shown that biting and pursuit seem to be controlled by different pathways from the CeA. So they decided to see if activating both pathways simultaneously (CeA to PCRt and CeA to PAG) could mimic the effects of stimulating the CeA itself. Indeed, they found that stimulating these two pathways together led the mice to robustly initiate attacks on artificial prey.

So what can we learn from this study? The scientists have demonstrated that the CeA acts as a command system for co-ordinating key behaviours for efficient hunting via two independent pathways. However, there are still some key questions remaining, for example, what determines whether the CeA sends those commands? The scientists hypothesise that cues such as the sight or smell of prey might cause the CeA to respond and send the command to elicit the appropriate motor actions. However, they can’t prove this in the current study.

Despite these limitations, this paper is a great example of how scientists can use cutting edge tools, like optogenetics, to tease apart the brain pathways responsible for different aspects of a complex behaviour such as hunting.

Post by: Michaela Loft

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