By Nicole Lim
Assistant Director, Communications & External Relations
Not content with solving the code to life, in his later years Nobel Laureate Francis Crick’s attention shifted to a new puzzle: the biological nature of consciousness. Together with neuroscientist Christof Koch, Crick hypothesised in a paper from his death bed, that consciousness occurs in a little known part of the brain called the claustrum.
The claustrum is a thin, irregular sheet of neurons deeply embedded beneath the cerebral cortex of both halves of the brain and is widely believed to be a multisensory integrator - a switchboard - that processes sensory inputs before sending out response signals to different parts of the brain. With connections throughout the brain, its exact function has long been a source for speculation with scientists attributing it a role in a range of behavioural, mental health and brain disorders. But because of its hard to reach location and sheet-like topography, these hypotheses, including Koch and Crick’s, remained just that.
All this is about to change. With advances in technology, particularly in the field of optogenetics, scientists are now able to study the claustrum in depth to determine its function. And that’s what LKCMedicine Professor of Neuroscience & Mental Health George Augustine plans to do with his recent Ministry of Education (MOE) Academic Research Funding (AcRF) Tier 2 grant. He was one of three scientists from LKCMedicine who received funding.
An LKCMedicine team, led by Prof George Augustine, is characterising the different kinds of neurons in the claustrum (circled) and their synaptic connections to shed light on the kind of information processed by this little-understood part of the brain that has long been suspected to be the seat of consciousness
Prof Augustine’s interest in the claustrum was sparked during a review of optogenetic probes expressed by his transgenic mice models in 2011. Each model expressed optogenetic probes in different neurons in the brain.
Prof Augustine said, “We were reviewing a long list, and suddenly, out popped a mouse that had a boat-load of expression in the claustrum. And my first reaction was ‘what is the claustrum?’”
This fortuitous discovery suggested a whole host of new opportunities. Using this transgenic model, Prof Augustine and his team started extensive physiology experiments to characterise the different kinds of neurons in the claustrum and their synaptic connections to each other.
With the AcRF grant, he now hopes to fully characterise all the neurons in the claustrum and complete an optogenetic map of the connections between them, finally shedding light on the kind of information the claustrum processes.
Within the three-year period of the grant, the team also aims to elucidate its function. Prof Augustine said, “It’s the dream project and we’re going straight for the jugular. We’re going to test the Crick and Koch hypothesis that the claustrum is central to consciousness.”
To determine this, the team will “switch” neurons in the claustrum of these mice on and off, before giving them a series of physical stimuli to determine whether consciousness has been affected. If the mice don’t respond (such as by pressing a lever) to multiple types of sensory stimuli, including visual, aural, olfactory and somatic stimuli, then they will be classed as unconscious. Prof Augustine said, “If we see the same response every time, we’ve perturbed consciousness.”
While this work is a long way off clinical application, if successful, it could provide a much deeper understanding of behaviour and yield insights into a wide range of mental health conditions and brain disorders, ranging from eating and mood disorders to schizophrenia, and Alzheimer’s and Parkinson’s disease.
Cancer and diabetes research also funded
Professor of Molecular Medicine Dean Nizetic and Assistant Professor of Metabolic Disease Yusuf Ali also received MOE AcRF Tier 2 grants.
Prof Nizetic’s project aims to elucidate the molecular mechanisms of clonal evolution in childhood leukaemia, the most common cancer in children; while Asst Prof Yusuf will investigate the role of the FIT2 protein within insulin-producing cells in physiological and obese/diabetic states.