Brain Waves

Accidents can sometimes spark innovation. About six years ago on a normal day in the lab, Western Sydney University neuroscientist, Yossi Buskila, was looking for signs of how brain diseases progress in sample slices taken from mice.

Brain slices typically only remain viable for around six hours before the cells die, so Buskila usually disposed of them at the end of his day. This time, he forgot. When he returned next morning, he was surprised to see that a small number of cells had survived.

“I asked myself, why did some survive, and can we enhance that process?” That led him and colleague, Paul Breen, from The MARCS Institute, to develop the ‘Braincubator’ — an incubation system that prolongs the slices’ longevity by up to six times, to around 36 hours. The apparatus opens new avenues of research into memory and learning, and into neurodegenerative disorders.

Buskila studies slices from mice that have been genetically modified to replicate how diseases such as Alzheimer’s, epilepsy and amyotrophic lateral sclerosis (ALS) affect electrical and chemical signals between the brain’s neuron and glial cells. He is also driven by a fundamental desire to reveal the brain’s workings. “How do brain-waves code information? How do thoughts come about?” Buskila says. “These questions are my passion.”

The short lifespan of a brain slice was a huge obstacle for research. Taking the brain out of the body and cutting into it immediately destroys 20-30% of cells. The rest become exposed to bacteria, which release toxins that kill cells within a few hours. And preparing new samples every morning took up to two hours.

Busilka’s braincubator preserves the slices in a tank filled with a liquid that mimics spinal fluid. Simply adding antibiotics to try to stop the bacteria growing will not work because the drugs would damage the brain cells. So Buskila’s team tried some other tricks. They found that cooling the slices to 15 or 16oC slowed the spread of bacteria.

Another way to destroy bacteria is to shine UV light on to the tank, but that also kills neurons. In the Braincubator, brain slices are kept in one cooled chamber, while in a second chamber, UV light shines on to the artificial spinal fluid which circulates between the two. This successfully slows bacterial growth in the liquid, dramatically increasing the slices’ life.

The Braincubator is already on sale and has proved useful for researchers. Dario Protti, a physiologist at the University of Sydney, uses the Braincubator in his lab, and says “it has had a very positive impact on my research”. He says the equipment helps reduce the number of animals used in experiments and could potentially be used to monitor changes in how proteins and genes are expressed in brain tissue over much longer periods.

“Now we can look at what happens not just in four hours, but in 20 hours, and study the difference between short-term and long-term synaptic processes,” says Buskila. “If the Braincubator can have a real impact on our understanding of how the brain works, that will make me happy.”