Neuroscience News Winter 2013 section

Directors Message Winter 2013
I am delighted to announce the establishment of Australias first Science of Learning Research Centre (SLRC) at UQ, an initiative led by QBI.

Directors Message Winter 2013

I am delighted to announce the establishment of Australia’s first Science of Learning Research Centre (SLRC) at UQ, an initiative led by QBI. The Centre will, for the first time, allow us to translate what we have discovered about how the brain learns into developing new ways to deliver learning in the classroom and elsewhere.

This idea has taken four years to come to fruition, having been first suggested to the Prime Minister’s Science, Engineering and Innovation Council in 2009 by an Expert Working Group of which I was a member.

This “benchtop to blackboard” approach is revolutionary for the learning community, and is led by Centre Director, Professor Ottmar Lipp from UQ’s School of Psychology, Professor Pankaj Sah from QBI, Professor John Hattie from the University of Melbourne, and Dr Mike Timms from ACER.

While our continued success in attaining competitive grant funding is vital to our ongoing research, equally important is the money we receive from our generous donors, whose valuable support allows us to more rapidly pursue and obtain our research goals, and ultimately, to develop new therapeutics to treat the enormous burden of neurological disease and mental ill health in our community.

This edition of Neuroscience News features a number of our key discoveries made over the past 12 months, which have been aided by philanthropic support.

Professor Perry Bartlett FAA
Director, Queensland Brain Institute

Events and Congratulations
  New Event Research Breakfast Series In April, QBI launched the “Research Breakfast Series”. These events aim to highlight the latest research findings in a more intimate setting,...

Events and Congratulations

 Heading off from QBI on the MND Ride to Conquer

New Event

Research Breakfast Series

In April, QBI launched the “Research Breakfast Series”. These events aim to highlight the latest research findings in a more intimate setting, allowing for greater interaction with those present.

Breakfast 1:  Schizophrenia

On Tuesday April 30, Professor John McGrath and Associate Professor Naomi Wray gave an insightful update on research and clinical advances in Schizophrenia. 

Schizophrenia is a poorly understood group of brain disorders, affecting about one in a hundred people. 

Professor McGrath and Associate Professor Wray focussed on new theories about the genetic factors and early life events that can contribute to the risk of this disorder. 

The breakfast was well-attended, with a full complement of 30 guests from the business sector, community care groups, as well as donors.

Like to attend?

Information on upcoming research breakfast talks is available by contacting Jenny Valentine on
j.valentine1@uq.edu.au
or (07) 3346 6413.

Recent Events

MND fundraising 

Ride to Conquer MND Update

On Friday May 3, UQ’s Senior Deputy Vice-Chancellor, Professor Debbie Terry, QBI Director Professor Perry Bartlett and a large crowd of supporters cheered on MND sufferers Scott Sullivan and Ian Davis as they embarked on the first leg of their 1000km journey from Brisbane to Sydney. 

Scott and Ian completed the gruelling ride in 16 days, with the goal of raising $250,000 for MND research. They are well on their way to meeting this target and funds raised will go toward supporting researchers into extending basic knowledge into the disease to better understand its cause and help identify where future therapies may play a role.

Souths Rugby Annual MND Fundraiser

QBI’s Dr Marie Mangelsdorf and Fabienne Alfonsi joined Australian Super Heavyweight Weightlifter, Damon Kelly, and former Wallabies and Queensland Reds player, Dan Crowley, as speakers at the annual MND Lunch at Souths Rugby Union Club on Friday May 17. The event raised over $10,000 to support the Ross Maclean Fellowship at QBI. 

Awards

Congratulations

Congratulations to Professor Linda Richards (above) who was awarded first place in the Vice-Chancellor’s Equity and Diversity Awards in recognition of all her work in establishing the Australian Brain Bee Challenge (ABBC). The competition, for high-school students in Australia and New Zealand, is aimed at encouraging students to learn more about the brain, and inspire them towards a career in science in general, and neuroscience in particular. 

Linda has dedicated considerable effort towards ensuring that as many students as possible are able to compete in the competition, with a particular focus on those in regional areas, or of Indigenous background, and it is this commitment to equity and diversity that earned her the award. 

Congratulations also go to PhD student, Fabio Cortesi, who has received a Mobility Fellowship from the Swiss National Science Foundation to work in the Marshall Laboratory at QBI. During his nine-month stay, Fabio will investigate the environmental cues for colour change and mimicry in a small marine fish as part of his project titled, Ecological and Molecular Basis for Mimicry in Vertebrates: Colour Plasticity and Adaptation in a Marine Fish.

Save the date

Soroptimist International Brisbane South Gala Art Exhibition: 11–16 July 2013

Funds raised go to motor neuron disease research at QBI. This is the sixth year they have had the exhibition to raise funds in memory of one of their members, Margaret Austin. Petrie Terrace Gallery, Unit 3, 162 Petrie Terrace, Brisbane. Please call Pam Grabbe on
0411 139 141 for more information.

Flies sleep like humans
QBI researchers have discovered that, like humans, flies sleep in stages of different intensities.

Flies sleep like humans

 : Dr Bart van Alphen working in the van Swinderen laboratory

QBI researchers have discovered that, like humans, flies sleep in stages of different intensities.

Associate Professor Bruno van Swinderen said that human sleep involved the rapid eye movement (REM) stage, or light sleep, during which dreaming typically occurred, and several stages of non-REM sleep, or deep sleep.

“We have shown that sleep in flies also appears to alternate between lighter and deeper sleep stages, suggesting different functions for each even in the smallest animal brains.”

The study, led by Dr Bart van Alphen, measured sleep intensity in flies by recording their brain activity and responsiveness to mechanical stimuli.

During waking behaviour and learning, some synaptic connections – the parts of the neurons that allow cell-to-cell communication – become strengthened.

One proposed function of deeper sleep stages is to proportionally weaken all synapses in the brain, so as to preserve learning while decreasing energy requirements.

The research group discovered that if they activated learning pathways during the day, the flies needed deeper sleep at night.

If they mutated a protein known to be important for weakening synapses, the flies compensated by sleeping more deeply even during the day.

“This suggests that synaptic weakening probably involves molecular processes that are engaged during deeper sleep stages,” Associate Professor van Swinderen said.

Fruit flies are being increasingly used as a model for studying the role of sleep in disease.

Associate Professor van Swinderen said that it is important to consider the importance of different stages of sleep in future studies of this kind.

A second study showed that a better understanding of sleep processes in the fly model might be relevant to general anaesthesia.

The study, led by Dr Benjamin Kottler, found that the brain circuits that promote sleep in the fly are also important for regulating sensitivity to a commonly used general anaesthetic, isoflurane.

Increasing activity of sleep-promoting neurons in the fly brain resulted in increased sensitivity to anaesthesia, while stimulating wake-promoting neurons results in resistance to anaesthesia.

That is, flies that slept more were hypersensitive to anaesthesia and those that slept less were resistant to anaesthesia.

Immature neurons important in a mature brain
A recent study has identified precisely when new neurons become important for learning.

Immature neurons important in a mature brain

 Activated neurons in the hippocampus. Image by Jana Vukovic

A recent study has identified precisely when new neurons become important for learning.

Lead researcher Dr Jana Vukovic said the study highlighted the contribution of neurons of different ages to different behaviours.

“New neurons are continually produced in the brain, passing through a number of developmental stages before becoming fully mature,” Dr Vukovic said.

The study assessed the role of new neurons born in a region of the brain known as the hippocampus.

“When we used a genetic technique to delete immature neurons in animal models, we found they had great difficulty learning a new spatial task.

“The new neurons appear particularly important for the brain to detect subtle but critical differences in the environment that can impact on the individual.”

The study, performed in QBI Director Professor Perry Bartlett’s laboratory, also demonstrates that these immature neurons, although required for learning, are not needed for memory retrieval.

“On the other hand, if the animals needed to remember a task they had already mastered in the past, before these immature neurons were deleted, their ability to perform the task was the same – so, they’ve remembered the task they learned earlier,” Dr Vukovic said.

This research allows for better understanding of the processes underlying learning and memory formation. 

Profile Professor Pankaj Sah
After training in medicine at The University of New South Wales and completing his internship, Professor Pankaj Sah did his PhD at The Australian National University (ANU).

Profile Professor Pankaj Sah

 Professor Pankaj Sah

After training in medicine at The University of New South Wales and completing his internship, Professor Pankaj Sah did his PhD at The Australian National University (ANU). 

Working with Professor Peter Gage on ion channel function in neurons, he discovered an interest in understanding how neurons in the brain communicate.

Following postdoctoral work at The University of California, San Francisco, and The University of Queensland (UQ), he established his own laboratory at the Department of Physiology at the University of Newcastle in 1994.;

He then joined the John Curtin School of Medical Research at ANU as a group leader in 1997.

In 2003, he was recruited to the Queensland Brain Institute at UQ, and was later appointed as Deputy Director (Research).

Professor Sah’s work has focussed on understanding the mechanisms that underlie learning and memory formation in the mammalian brain.

He is primarily interested in the amygdala – a region important in processing emotions, in particular, assigning emotional significance to sensory stimuli.

Professor Sah’s laboratory is known for studying the amygdala using a combination of molecular tools, electrophysiology, anatomical reconstruction and calcium imaging. 

To date the laboratory has focussed on using animal models, however, they are now collaborating with neurologist Professor Peter Silburn, making recordings from patients undergoing electrode placement for deep brain stimulation to treat a variety of disorders such as Parkinson’s disease, Tourette’s syndrome and essential tremor.

Most recently, Professor Sah was one of the key members involved in leading a successful grant application, which resulted in $16 million in funding from the Australian Research Council to support the Science of Learning Research Centre (SLRC).

The SLRC brings together neuroscientists, cognitive psychologists and experts in education to understand the learning process.

“This collaboration is unique and will establish new collaborations between scientists working at the bench to understand learning and educators working in classroom to deliver education. This work will be harnessed to design new and practical teaching and classroom assessment tools,” Professor Sah explained.

“It is an exciting new time for neuroscience and our understanding of how the brain learns and responds. These discoveries will not only provide new insights into the treatment of brain disorders but will drive new ways to deliver and assess education in the future.”

QBI to help pave a new pathway for education
QBI forms part of a consortium awarded $16 million over four years from the Australian Research Council (ARC) for a Science of Learning Research Centre (SLRC).

QBI to help pave a new pathway for education

QBI forms part of a consortium awarded $16 million over four years from the Australian Research Council (ARC) for a Science of Learning Research Centre (SLRC).

The Special Research Initiative funding, announced in May, will bring together researchers in neuroscience, education and cognitive psychology from three lead institutions, The University of Queensland (UQ), the University of Melbourne (UMelb), and the Australian Council for Educational Research (ACER).

They will be joined by researchers from the partner organisations of Flinders University, Deakin University, University of New England, Charles Darwin University and Macquarie University, all of whom will work with teachers to enhance our understanding of the learning process.

The grant comes four years after the concept was initially recommended by the Prime Minister’s Science, Engineering and Innovation Council Expert Working Group, which included QBI Director Professor Perry Bartlett, in their report, Transforming Learning and the Transmission of Knowledge.

This collaboration will establish new means to assess the impact of different types of learning and strategies to inform teaching practices to benefit all Australians.

The grant was led by Professor Ottmar Lipp from UQ’s School of Psychology, in cooperation with Professor Pankaj Sah (QBI), Professor John Hattie (UMelb), and Dr Mike Timms (ACER).

Professor Lipp says the Centre will place learning at the focus of its research and will develop an evidence-based approach to educational practice.

“It is essential that this is done in collaboration between researchers from different disciplines on the one side and practitioners on the other. 

“This collaboration will be facilitated by research done in two experimental classrooms, the “centrepieces” of the SLRC, one at The University of Queensland and one at the University of Melbourne”.

In addition to the eight research organisations, the Centre is supported by nine partner organisations, including Education Queensland, the Victorian Department of Education and Early Childhood Development, the South Australian Department of Education and Child Development, Questacon, North Carolina State University, Institute of Education (London), Carnegie Mellon University, University College London, and the Benevolent Society.

Queensland research holds promise for patients with spinal cord injury
QBI Director and study co-leader, Professor Perry Bartlett said the research was extremely exciting and both confirmed and extended previous studies showing that blocking the action of the receptor EphA4 prevented the loss of nerve tissue following i...

Queensland research holds promise for patients with spinal cord injury

 Some members of the team working on EphA4 (L-R) Professor Andrew Boyd, Ms Sophie Tajouri and  Professor Perry Bartlett.

In a joint study, researchers at QBI, together with colleagues at the Queensland Institute of Medical Research (QIMR) and the University of Melbourne, have advanced a potential new treatment for spinal cord injury with a view to starting clinical trials.

The collaboration showed that blocking a specific protein could make a dramatic difference to the balance and limb coordination of rats with spinal injuries.

QBI Director and study co-leader, Professor Perry Bartlett said the research was extremely exciting and both confirmed and extended previous studies showing that blocking the action of the receptor EphA4 prevented the loss of nerve tissue following injury and promoted repair. 

Professor Bartlett and QIMR’s Professor Andrew Boyd first identified the role of EphA4 in 1998 when they showed that the receptor was critical to the development of the nerves that control walking and other complex muscle functions. 

Subsequent studies showed that after spinal cord injury, the production of the EphA4 protein was increased and this protein was acting to stop severed nerve endings from regrowing through the injury site. 

Professor Boyd’s laboratory at QIMR, working with Professor Bartlett’s laboratory at QBI, then developed a “decoy” protein to block EphA4 function. 

Treatment with the EphA4 blocker has been used to improve recovery of function after spinal cord injury in animals.

“That first discovery back in 1998 opened up a clear path to a potential treatment for any diseases or injuries involving motor nerves,” Professor Boyd said.

“The idea would be to use the “decoy” treatment immediately after spinal cord injury to try to improve the patient’s recovery. 

“And as a neurologist or neurosurgeon will tell you, if you could improve function even marginally for a quadriplegic, you will make a massive difference to their life.” 

Chair of SpinalCure Australia, Ms Joanna Knott, says the news is promising.

“This news is extremely encouraging in the spinal cord injury field and we have followed the discoveries of the EphA4 receptor with interest.

“This team of researchers will certainly put Australia on the map, especially when the clinical trial begins.” 

In addition to NHMRC and ARC funding, this research was supported by funding from the Lisa Palmer Spinal Research Consortium and SpinalCure Australia. 

Recognition of the support of QBIs friends and donors
Without the support of QBIs friends and donors, the significant discoveries we have made during the past 12 months, some of which are highlighted here, would not have been possible.

Recognition of the support of QBIs friends and donors

 Visitors to QBI on 2013 Dementia Awareness Day  discuss the topic with researcher Tishila Palliyaguru.

Without the support of QBI’s friends and donors, the significant discoveries we have made during the past 12 months, some of which are highlighted below, would not have been possible. 

We are confident that we will continue to make new discoveries, but your contributions will more rapidly assist with completion and clinical translation.

To donate please visit www.qbi.uq.edu.au/how-to-donate-to-qbi

MRI scans being used as a diagnostic tool for Alzheimer’s detection 

Scientists may now be able to detect early features of Alzheimer’s disease using magnetic resonance imaging (MRI).

Using MRI, Associate Professor Elizabeth Coulson and her team were able to detect degeneration of basal forebrain cholinergic neurons – an early and key feature of Alzheimer’s disease. 

“Traditional methods of detecting changes to the brain in Alzheimer’s disease by MRI require tissue to have undergone significant degeneration such that there is atrophy or loss of the tissue, ” says Associate Professor Coulson.

Her team has now determined that early neurodegenerative changes in the basal forebrain can be detected in an animal model using a non-invasive method of MRI called diffusion tensor imaging (DTI).

“By doing this, we were able to pinpoint significant signs of Alzheimer’s onset, before the basal forebrain cells had actually deteriorated,” Associate Professor Coulson said.

“This could allow patients the opportunity to receive treatment to either reduce the effects or cease the onset of Alzheimer’s.” 

Scientists are now looking to use DTI to detect these early signs of Alzheimer’s disease in humans. 

“These findings provide increased support for using DTI and probabilistic tractography for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer’s disease,” Associate Professor Coulson said. 

Scientists clearer on gene linked to motor neuron disease

QBI’s scientists are closer to developing a therapeutic target for neurodegenerative disorders, including motor neuron disease (MND).

The study monitored the functions of the protein TDP-43 in the nervous system, which until now have been largely unknown.

An expert in MND and contributor to the study, Dr Marie Manglesdorf, says the analysis produced a list of 1,839 potential TDP-43 gene targets, many of which overlap with previous studies.

“In the past we have known TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport, however, we haven’t been able to precisely pinpoint the genes it controls,” Dr Mangelsdorf said.

“By understanding the role TDP-43 plays in maintaining connections between nerve and muscle cells and the genes it controls, we can work towards developing therapeutic interventions to delay or eliminate deterioration of the gene.”

QBI’s research into MND is made possible thanks to the Ross Maclean Senior Research Fellowship, the Peter Goodenough Bequest and the MND and Me Foundation Ltd.

New insights into learning and memory

Work from Professor Perry Bartlett’s laboratory has shown, for the first time, that the brain cells usually responsible for mediating immunity, microglia, have an inhibitory effect on memory during ageing.

The discovery, published in The Journal of Neuroscience, came after postdoctoral researcher Dr Jana Vukovic observed that the increased production of new neurons in mice that were actively running was due to the release of fractalkine in the hippocampus – the brain structure responsible for specific types of learning and memory.

Professor Bartlett said it had been known for some time that exercise increased the production of new nerve cells in the hippocampus in young and even aged mice.

“But this study found that it is fractalkine that appears to be specifically mediating this effect by making the microglia produce factors that activate the stem cells that produce new nerve cells,” he said.

“Once the cells are activated they divide and produce new cells, which underpin the animal’s ability to learn and form memories. This means that fractalkine may form the basis for the development of future therapies.

“The discovery is especially exciting because we have found that older animals suffering cognitive decline showed significantly lower levels of fractalkine.

“We are seeking ways of increasing fractalkine levels in patients with cognitive decline, and hoping this may be a new frontline therapy in treating dementia.”

Dr Vukovic said that until relatively recently, it was thought the adult brain was incapable of generating new neurons.

“But work from Professor Bartlett’s laboratory over the past 20 years has demonstrated that the brains of adult animals retain the ability to make new nerve cells,” she said.

“The challenge is to find out how to stimulate this production in the aged animal and human where production has slowed.”

The latest work was a significant step toward understanding the molecular mechanism that may impair learning and memory in the ageing population.