“Destroying neurons in the zona incerta leads to weight reduction”
[ C H R O N I C L E ]
Resisting a succulent crème brulée or suppressing a craving for chocolate... Who has never dreamt of having access to a central button in the brain to switch off greedy impulses, like in the animated film Inside Out? Be under no illusion! The aim of this chronicle is not to propose solutions for losing weight before the holidays, but to share with you the latest knowledge on the brain mechanisms that govern our desire to eat. Neuroscientists at the American Yale University recently identified the above-mentioned button, and the mechanism by which our brain triggers food intake (1).
As often with behavioural neurosciences, studying pathological behaviours can shed light on the normal operation of our brains. The authors of this study looked at binge eating, a disorder characterised by repeated consumption of very large quantities of food. In particular fatty foods and foods that provide a pleasant sensation, such as our crème brulée.
Scientists launched the study after observing this compulsive attitude in patients suffering from Parkinson’s disease who had undergone deep brain stimulation. This therapy consists of implanting electrodes into the brain and stimulating it by means of electrical impulses. While this treatment reduced the motor issues associated with the disease, it may also lead to unwanted side effects. Thus, stimulating the subthalamic nucleus, the brain region involved in action selection, triggered the action of eating in some patients!
In the absence of electrical stimulation however, where does the food impulse come from? Ironically, the Yale neuroscientists located it in the zona incerta, one of the least studied regions of the brain, despite its strong connections to the rest of the brain. To understand the role of this mysterious region in eating disorders, they used a set of elegant in vivo techniques (in mice models) to test specific groups of neurons in several regions of the brain.
In particular, they used an optogenetic method. The principle? By inoculating viral vectors, viruses that cannot spread but that can modify the genetic material of the target neurons to make them photosensitive. Result: they activate in the presence of light, which acts like a switch on the neurones. By emitting light in the zona incerta, scientists showed that activating neurones in this area very rapidly increased the mice’s food intake. It is incredible to see how voraciously these rodents gobble down the food whenever the light is emitted! On the contrary, destroying neurons in the zona incerta leads to a reduction in body weight.
The beauty of the study lies in the discovery of a brain circuit responsible for this excessive eating. By using other viral vectors derived from the rabies virus, scientists showed that activating neurones in the zona increta reduced the activity of another type of neuron located in the paraventricular thalamus, already known for its role in controlling our eating impulses. As soon as this region receives an inhibition message from the zona incerta, the beast is set free, and the appetite becomes uncontrollable.
This study has far-reaching implications, as eating disorders are not only limited to patients treated with deep brain stimulation. They are associated with a wide range of psychiatric disorders and already represent a challenge for public health. In this context, identifying the circuit responsible for our desire to eat opens up new treatment avenues. And fundamentally, feeds our hunger... for knowledge!
(1) X. Zhang et A. N. Van den Pol, Science, 356, 853, 2017.
Mariana Alonso is a neuroscientist at the Laboratory of Perception and Memory at Institut Pasteur. Her work looks into neurogenesis and brain plasticity in adults, the neuronal bases of smell linked to behaviour and the relationships between the microbiota, immunity and the brain.