To understand what drives people to overeat, scientists are looking more closely at a brain structure involved in motivation, called the nucleus accumbens. This small region drives reward-seeking behaviors underlying the pursuit of sex, recreational drugs like nicotine and alcohol, and food.

“These brain motivation centers evolved to help us survive; finding food and having sex are essential to the survival of an individual and of a species,” said Carrie Ferrario, Ph.D., associate professor in the Department of Pharmacology at U-M Medical School.

“What was advantageous when food was hard to find has become a disadvantage and unhealthy in the current food dense environment. This is compounded by the over-abundance of over-processed, low nutrition foods that may satisfy our taste but leave our bodies unnourished. People don’t tend to find it difficult to turn down an extra serving of broccoli, but just one more french-fry or making room for a bit of chocolate dessert…that’s a different story. The real challenge is overcoming these urges and changing our behavior when it comes to food,” Ferrario added.

Given the immense toll obesity takes on virtually all body systems, Ferrario, Peter Vollbrecht, Ph.D., of Western Michigan University, and their colleagues are using rat models to understand potential brain differences between animals who are prone to over-eating and obesity and those who are not.

Previous research from Ferrario’s lab pinpointed differences in the nucleus accumbens in obesity-prone and obesity-resistant rats. Their latest study, published in the Journal of Neurochemistry, tracked what was happening in real time in the brain when these animals were presented with glucose, a type of sugar, labeled with a tracer. The tracer allowed the researchers to measure this new sugar in the brain.

Sugar is the brain’s main fuel source and once there, the molecule is broken down and used to create new molecules such as glutamine, glutamate, and GABA, each with an important role in influencing the activation of neurons in the brain and nervous system.

“Glucose that is consumed gets broken down and then its carbons get incorporated into neurotransmitters. We see those labelled carbons showing up in those molecules — glutamate, glutamine, and GABA — over time,” explained Vollbrecht.

They found that glucose was taking longer to get into the nucleus accumbens of obesity-prone animals.

Furthermore, when measuring the concentration of the glutamate, glutamine, and GABA, they discovered excess levels of glutamate, an excitatory neurotransmitter. This, said the team, implied a defect in a neurotransmitter recycling process, typically maintained in the nervous system by star-shaped cells called astrocytes.

Normally, astrocytes will pull glutamate out of the space between neurons, called the synapse, convert it into glutamine, and then shuttle it back to cells that produce GABA or glutamate. This sequence is crucial for turning neurons off and on. “The findings suggest that we’re getting too much glutamate and it’s not being taken out of the synapse,” said Vollbrecht.

Ferrario added, “The balance between glutamate and GABA (the main inhibitory transmitter) is really important for brain function and will influence activity of the neurons in the nucleus accumbens.”

This balance, and therefore brain activity, is different in obesity-prone vs. obesity-resistant rats.

The fact that these rats are either prone to obesity or not is important for disentangling cause and effect, says Vollbrecht. “It allows us to remove diet as one of the variables.”

The team hopes to next study the role of inflammation in the development of obesity, and how differences in brain function contribute to susceptibility and resistance to obesity.

The new form of ice is amorphous. Unlike ordinary crystalline ice where the molecules arrange themselves in a regular pattern, in amorphous ice the molecules are in a disorganised form that resembles a liquid.

In this paper, published in Science, the team created a new form of amorphous ice in experiment and achieved an atomic-scale model of it in computer simulation. The experiments used a technique called ball-milling, which grinds crystalline ice into small particles using metal balls in a steel jar. Ball-milling is regularly used to make amorphous materials, but it had never been applied to ice.

The team found that ball-milling created a novel amorphous form of ice, which unlike all other known ices, had a density similar to that of liquid water and whose state resembled water in solid form. They named the new ice medium-density amorphous ice (MDA).

To understand the process at the molecular scale the team employed computational simulation. By mimicking the ball-milling procedure via repeated random shearing of crystalline ice, the team successfully created a computational model of MDA.

“Our discovery of MDA raises many questions on the very nature of liquid water and so understanding MDA’s precise atomic structure is very important” comments co-author Dr. Michael Davies, who carried out the computational modelling. “We found remarkable similarities between MDA and liquid water.”

A happy medium

Amorphous ices have been suggested to be models for liquid water. Until now, there have been two main types of amorphous ice: high-density and low-density amorphous ice.

As the names suggest, there is a large density gap between them. This density gap, combined with the fact that the density of liquid water lies in the middle, has been a cornerstone of our understanding of liquid water. It has led in part to the suggestion that water consists of two liquids: one high- and one low-density liquid.

Senior author Professor Christoph Salzmann said: “The accepted wisdom has been that no ice exists within that density gap. Our study shows that the density of MDA is precisely within this density gap and this finding may have far-reaching consequences for our understanding of liquid water and its many anomalies.”

A high-energy geophysical material

The discovery of MDA gives rise to the question: where might it exist in nature? Shear forces were discovered to be key to creating MDA in this study. The team suggests ordinary ice could undergo similar shear forces in the ice moons due to the tidal forces exerted by gas giants such as Jupiter.

Moreover, MDA displays one remarkable property that is not found in other forms of ice. Using calorimetry, they found that when MDA recrystallises to ordinary ice it releases an extraordinary amount of heat. The heat released from the recrystallization of MDA could play a role in activating tectonic motions. More broadly, this discovery shows water can be a high-energy geophysical material.

Prof. Angelos Michaelides, lead author from Cambridge, said: “Amorphous ice in general is said to be the most abundant form of water in the universe. The race is now on to understand how much of it is MDA and how geophysically active MDA is.”